STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells
Identifieur interne : 000401 ( Pmc/Checkpoint ); précédent : 000400; suivant : 000402STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells
Auteurs : Xiaoyan Shao [République populaire de Chine] ; Xueke Wang [République populaire de Chine] ; Xianling Guo [République populaire de Chine] ; Ke Jiang [République populaire de Chine] ; Tian Ye [République populaire de Chine] ; Jianhua Chen [République populaire de Chine] ; Juemin Fang [République populaire de Chine] ; Linaer Gu [République populaire de Chine] ; Sitong Wang [République populaire de Chine] ; Guirong Zhang [République populaire de Chine] ; Songshu Meng [République populaire de Chine] ; Qing Xu [République populaire de Chine]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2019.
Abstract
Url:
DOI: 10.3389/fonc.2019.00436
PubMed: 31192135
PubMed Central: 6548873
Affiliations:
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PMC:6548873Le document en format XML
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Wang, Xueke" sort="Wang, Xueke" uniqKey="Wang X" first="Xueke" last="Wang">Xueke Wang</name>
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<author><name sortKey="Guo, Xianling" sort="Guo, Xianling" uniqKey="Guo X" first="Xianling" last="Guo">Xianling Guo</name>
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<author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Ye, Tian" sort="Ye, Tian" uniqKey="Ye T" first="Tian" last="Ye">Tian Ye</name>
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<author><name sortKey="Chen, Jianhua" sort="Chen, Jianhua" uniqKey="Chen J" first="Jianhua" last="Chen">Jianhua Chen</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Fang, Juemin" sort="Fang, Juemin" uniqKey="Fang J" first="Juemin" last="Fang">Juemin Fang</name>
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,<addr-line>Shanghai</addr-line>
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,<addr-line>Shanghai</addr-line>
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<author><name sortKey="Gu, Linaer" sort="Gu, Linaer" uniqKey="Gu L" first="Linaer" last="Gu">Linaer Gu</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Wang, Sitong" sort="Wang, Sitong" uniqKey="Wang S" first="Sitong" last="Wang">Sitong Wang</name>
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,<addr-line>Shanghai</addr-line>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name>
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<author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name>
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<author><name sortKey="Xu, Qing" sort="Xu, Qing" uniqKey="Xu Q" first="Qing" last="Xu">Qing Xu</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells</title>
<author><name sortKey="Shao, Xiaoyan" sort="Shao, Xiaoyan" uniqKey="Shao X" first="Xiaoyan" last="Shao">Xiaoyan Shao</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Wang, Xueke" sort="Wang, Xueke" uniqKey="Wang X" first="Xueke" last="Wang">Xueke Wang</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Guo, Xianling" sort="Guo, Xianling" uniqKey="Guo X" first="Xianling" last="Guo">Xianling Guo</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Ye, Tian" sort="Ye, Tian" uniqKey="Ye T" first="Tian" last="Ye">Tian Ye</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chen, Jianhua" sort="Chen, Jianhua" uniqKey="Chen J" first="Jianhua" last="Chen">Jianhua Chen</name>
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,<addr-line>Shanghai</addr-line>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Fang, Juemin" sort="Fang, Juemin" uniqKey="Fang J" first="Juemin" last="Fang">Juemin Fang</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Tongji University Cancer Center</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gu, Linaer" sort="Gu, Linaer" uniqKey="Gu L" first="Linaer" last="Gu">Linaer Gu</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Tongji University Cancer Center</institution>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author><name sortKey="Wang, Sitong" sort="Wang, Sitong" uniqKey="Wang S" first="Sitong" last="Wang">Sitong Wang</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Tongji University Cancer Center</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Central laboratory, Cancer School of Medicine, Liaoning Cancer Hospital and Institute, Hospital of China Medical University</institution>
,<addr-line>Shenyang</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Dalian Medical University Cancer Center, Institute of Cancer Stem Cell</institution>
,<addr-line>Dalian</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Xu, Qing" sort="Xu, Qing" uniqKey="Xu Q" first="Qing" last="Xu">Qing Xu</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Tongji University Cancer Center</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in Oncology</title>
<idno type="eISSN">2234-943X</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><bold>Background:</bold>
Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated.</p>
<p><bold>Methods:</bold>
Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors.</p>
<p><bold>Results:</bold>
Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth.</p>
<p><bold>Conclusions:</bold>
Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Oncol</journal-id>
<journal-id journal-id-type="iso-abbrev">Front Oncol</journal-id>
<journal-id journal-id-type="publisher-id">Front. Oncol.</journal-id>
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<issn pub-type="epub">2234-943X</issn>
<publisher><publisher-name>Frontiers Media S.A.</publisher-name>
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</journal-meta>
<article-meta><article-id pub-id-type="pmid">31192135</article-id>
<article-id pub-id-type="pmc">6548873</article-id>
<article-id pub-id-type="doi">10.3389/fonc.2019.00436</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Oncology</subject>
<subj-group><subject>Original Research</subject>
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<title-group><article-title>STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells</article-title>
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<xref ref-type="aff" rid="aff1"><sup>1</sup>
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<xref ref-type="aff" rid="aff2"><sup>2</sup>
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<xref ref-type="aff" rid="aff3"><sup>3</sup>
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<xref ref-type="author-notes" rid="fn002"><sup>†</sup>
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<xref ref-type="aff" rid="aff2"><sup>2</sup>
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<xref ref-type="aff" rid="aff3"><sup>3</sup>
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<xref ref-type="author-notes" rid="fn002"><sup>†</sup>
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</contrib>
<contrib contrib-type="author"><name><surname>Jiang</surname>
<given-names>Ke</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/525662/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Ye</surname>
<given-names>Tian</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Jianhua</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fang</surname>
<given-names>Juemin</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gu</surname>
<given-names>Linaer</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Sitong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Guirong</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meng</surname>
<given-names>Songshu</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
<xref ref-type="corresp" rid="c002"><sup>*</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/382145/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Qing</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="c003"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
<institution>Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</aff>
<aff id="aff2"><sup>2</sup>
<institution>Department of Oncology, Dermatology Hospital, TongJi University</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</aff>
<aff id="aff3"><sup>3</sup>
<institution>Tongji University Cancer Center</institution>
,<addr-line>Shanghai</addr-line>
,<country>China</country>
</aff>
<aff id="aff4"><sup>4</sup>
<institution>Dalian Medical University Cancer Center, Institute of Cancer Stem Cell</institution>
,<addr-line>Dalian</addr-line>
,<country>China</country>
</aff>
<aff id="aff5"><sup>5</sup>
<institution>Central laboratory, Cancer School of Medicine, Liaoning Cancer Hospital and Institute, Hospital of China Medical University</institution>
,<addr-line>Shenyang</addr-line>
,<country>China</country>
</aff>
<author-notes><fn fn-type="edited-by"><p>Edited by: Matiullah Khan, AIMST University, Malaysia</p>
</fn>
<fn fn-type="edited-by"><p>Reviewed by: Oliver Kepp, Institut Gustave Roussy, France; Karishma Rajani, Mayo Clinic, United States</p>
</fn>
<corresp id="c001">*Correspondence: Guirong Zhang <email>zhang.lth@163.com</email>
</corresp>
<corresp id="c002">Songshu Meng <email>ssmeng@dmu.edu.cn</email>
</corresp>
<corresp id="c003">Qing Xu <email>xuqingmd@tongji.edu.cn</email>
</corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology</p>
</fn>
<fn fn-type="other" id="fn002"><p>†These authors have contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>29</day>
<month>5</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>9</volume>
<elocation-id>436</elocation-id>
<history><date date-type="received"><day>29</day>
<month>1</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>07</day>
<month>5</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2019 Shao, Wang, Guo, Jiang, Ye, Chen, Fang, Gu, Wang, Zhang, Meng and Xu.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Shao, Wang, Guo, Jiang, Ye, Chen, Fang, Gu, Wang, Zhang, Meng and Xu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract><p><bold>Background:</bold>
Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated.</p>
<p><bold>Methods:</bold>
Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors.</p>
<p><bold>Results:</bold>
Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth.</p>
<p><bold>Conclusions:</bold>
Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.</p>
</abstract>
<kwd-group><kwd>newcastle disease virus</kwd>
<kwd>immunogenic cell death</kwd>
<kwd>melanoma</kwd>
<kwd>signal transducer and activator of transcription 3</kwd>
<kwd>virotherapy</kwd>
</kwd-group>
<funding-group><award-group><funding-source id="cn001">Science and Technology Commission of Shanghai Municipality<named-content content-type="fundref-id">10.13039/501100003399</named-content>
</funding-source>
<award-id rid="cn001">16431903202</award-id>
<award-id rid="cn001">17411967300</award-id>
<award-id rid="cn001">18DZ1910102</award-id>
</award-group>
<award-group><funding-source id="cn002">National Natural Science Foundation of China<named-content content-type="fundref-id">10.13039/501100001809</named-content>
</funding-source>
<award-id rid="cn002">81372471</award-id>
<award-id rid="cn002">81502674</award-id>
<award-id rid="cn002">81702311</award-id>
<award-id rid="cn002">81772905</award-id>
<award-id rid="cn002">81803090</award-id>
</award-group>
<award-group><funding-source id="cn003">Shanghai Municipal Population and Family Planning Commission<named-content content-type="fundref-id">10.13039/501100008410</named-content>
</funding-source>
<award-id rid="cn003">201640020</award-id>
<award-id rid="cn003">2016LP029</award-id>
</award-group>
<award-group><funding-source id="cn004">Shanghai Hospital Development Center<named-content content-type="fundref-id">10.13039/501100008750</named-content>
</funding-source>
<award-id rid="cn004">16CR3072B</award-id>
</award-group>
<award-group><funding-source id="cn005">Natural Science Foundation of Liaoning Province<named-content content-type="fundref-id">10.13039/501100005047</named-content>
</funding-source>
<award-id rid="cn005">2015020655</award-id>
</award-group>
</funding-group>
<counts><fig-count count="6"></fig-count>
<table-count count="0"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="72"></ref-count>
<page-count count="14"></page-count>
<word-count count="8259"></word-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Shao, Xiaoyan" sort="Shao, Xiaoyan" uniqKey="Shao X" first="Xiaoyan" last="Shao">Xiaoyan Shao</name>
</noRegion>
<name sortKey="Chen, Jianhua" sort="Chen, Jianhua" uniqKey="Chen J" first="Jianhua" last="Chen">Jianhua Chen</name>
<name sortKey="Chen, Jianhua" sort="Chen, Jianhua" uniqKey="Chen J" first="Jianhua" last="Chen">Jianhua Chen</name>
<name sortKey="Chen, Jianhua" sort="Chen, Jianhua" uniqKey="Chen J" first="Jianhua" last="Chen">Jianhua Chen</name>
<name sortKey="Fang, Juemin" sort="Fang, Juemin" uniqKey="Fang J" first="Juemin" last="Fang">Juemin Fang</name>
<name sortKey="Fang, Juemin" sort="Fang, Juemin" uniqKey="Fang J" first="Juemin" last="Fang">Juemin Fang</name>
<name sortKey="Fang, Juemin" sort="Fang, Juemin" uniqKey="Fang J" first="Juemin" last="Fang">Juemin Fang</name>
<name sortKey="Gu, Linaer" sort="Gu, Linaer" uniqKey="Gu L" first="Linaer" last="Gu">Linaer Gu</name>
<name sortKey="Gu, Linaer" sort="Gu, Linaer" uniqKey="Gu L" first="Linaer" last="Gu">Linaer Gu</name>
<name sortKey="Gu, Linaer" sort="Gu, Linaer" uniqKey="Gu L" first="Linaer" last="Gu">Linaer Gu</name>
<name sortKey="Guo, Xianling" sort="Guo, Xianling" uniqKey="Guo X" first="Xianling" last="Guo">Xianling Guo</name>
<name sortKey="Guo, Xianling" sort="Guo, Xianling" uniqKey="Guo X" first="Xianling" last="Guo">Xianling Guo</name>
<name sortKey="Guo, Xianling" sort="Guo, Xianling" uniqKey="Guo X" first="Xianling" last="Guo">Xianling Guo</name>
<name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name>
<name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name>
<name sortKey="Shao, Xiaoyan" sort="Shao, Xiaoyan" uniqKey="Shao X" first="Xiaoyan" last="Shao">Xiaoyan Shao</name>
<name sortKey="Shao, Xiaoyan" sort="Shao, Xiaoyan" uniqKey="Shao X" first="Xiaoyan" last="Shao">Xiaoyan Shao</name>
<name sortKey="Wang, Sitong" sort="Wang, Sitong" uniqKey="Wang S" first="Sitong" last="Wang">Sitong Wang</name>
<name sortKey="Wang, Sitong" sort="Wang, Sitong" uniqKey="Wang S" first="Sitong" last="Wang">Sitong Wang</name>
<name sortKey="Wang, Sitong" sort="Wang, Sitong" uniqKey="Wang S" first="Sitong" last="Wang">Sitong Wang</name>
<name sortKey="Wang, Xueke" sort="Wang, Xueke" uniqKey="Wang X" first="Xueke" last="Wang">Xueke Wang</name>
<name sortKey="Wang, Xueke" sort="Wang, Xueke" uniqKey="Wang X" first="Xueke" last="Wang">Xueke Wang</name>
<name sortKey="Wang, Xueke" sort="Wang, Xueke" uniqKey="Wang X" first="Xueke" last="Wang">Xueke Wang</name>
<name sortKey="Xu, Qing" sort="Xu, Qing" uniqKey="Xu Q" first="Qing" last="Xu">Qing Xu</name>
<name sortKey="Xu, Qing" sort="Xu, Qing" uniqKey="Xu Q" first="Qing" last="Xu">Qing Xu</name>
<name sortKey="Xu, Qing" sort="Xu, Qing" uniqKey="Xu Q" first="Qing" last="Xu">Qing Xu</name>
<name sortKey="Ye, Tian" sort="Ye, Tian" uniqKey="Ye T" first="Tian" last="Ye">Tian Ye</name>
<name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name>
</country>
</tree>
</affiliations>
</record>
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