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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interleukin-8 Can Reduce Post-Surgical Lymphedema Formation by Promoting Lymphatic Vessel Regeneration</title><author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Yong Suk" sort="Lee, Yong Suk" uniqKey="Lee Y" first="Yong Suk" last="Lee">Yong Suk Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Chung, Hee Kyoung" sort="Chung, Hee Kyoung" uniqKey="Chung H" first="Hee Kyoung" last="Chung">Hee Kyoung Chung</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name><affiliation><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Ha Neul" sort="Lee, Ha Neul" uniqKey="Lee H" first="Ha Neul" last="Lee">Ha Neul Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Kim, Kyu Eui" sort="Kim, Kyu Eui" uniqKey="Kim K" first="Kyu Eui" last="Kim">Kyu Eui Kim</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Park, Eun Kyung" sort="Park, Eun Kyung" uniqKey="Park E" first="Eun Kyung" last="Park">Eun Kyung Park</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Maeng, Yong Sun" sort="Maeng, Yong Sun" uniqKey="Maeng Y" first="Yong Sun" last="Maeng">Yong Sun Maeng</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Kim, Nam Yun" sort="Kim, Nam Yun" uniqKey="Kim N" first="Nam Yun" last="Kim">Nam Yun Kim</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Ladner, Robert D" sort="Ladner, Robert D" uniqKey="Ladner R" first="Robert D." last="Ladner">Robert D. Ladner</name><affiliation><nlm:aff id="A2">Department of Pathology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Petasis, Nicos A" sort="Petasis, Nicos A" uniqKey="Petasis N" first="Nicos A." last="Petasis">Nicos A. Petasis</name><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Chemistry, Dornsife College of Letters, Arts & Sciences, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name><affiliation><nlm:aff id="A7">Division of Pediatric Urology, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><affiliation><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, California</nlm:aff></affiliation></author><author><name sortKey="Lenz, Heinz Josef" sort="Lenz, Heinz Josef" uniqKey="Lenz H" first="Heinz-Josef" last="Lenz">Heinz-Josef Lenz</name><affiliation><nlm:aff id="A3">Division of Medical Oncology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22945845</idno><idno type="pmc">4166493</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166493</idno><idno type="RBID">PMC:4166493</idno><idno type="doi">10.1007/s10456-012-9297-6</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">003A64</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003A64</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Interleukin-8 Can Reduce Post-Surgical Lymphedema Formation by Promoting Lymphatic Vessel Regeneration</title><author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Yong Suk" sort="Lee, Yong Suk" uniqKey="Lee Y" first="Yong Suk" last="Lee">Yong Suk Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Chung, Hee Kyoung" sort="Chung, Hee Kyoung" uniqKey="Chung H" first="Hee Kyoung" last="Chung">Hee Kyoung Chung</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name><affiliation><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Ha Neul" sort="Lee, Ha Neul" uniqKey="Lee H" first="Ha Neul" last="Lee">Ha Neul Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Kim, Kyu Eui" sort="Kim, Kyu Eui" uniqKey="Kim K" first="Kyu Eui" last="Kim">Kyu Eui Kim</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Park, Eun Kyung" sort="Park, Eun Kyung" uniqKey="Park E" first="Eun Kyung" last="Park">Eun Kyung Park</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Maeng, Yong Sun" sort="Maeng, Yong Sun" uniqKey="Maeng Y" first="Yong Sun" last="Maeng">Yong Sun Maeng</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Kim, Nam Yun" sort="Kim, Nam Yun" uniqKey="Kim N" first="Nam Yun" last="Kim">Nam Yun Kim</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Ladner, Robert D" sort="Ladner, Robert D" uniqKey="Ladner R" first="Robert D." last="Ladner">Robert D. Ladner</name><affiliation><nlm:aff id="A2">Department of Pathology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Petasis, Nicos A" sort="Petasis, Nicos A" uniqKey="Petasis N" first="Nicos A." last="Petasis">Nicos A. Petasis</name><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Chemistry, Dornsife College of Letters, Arts & Sciences, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name><affiliation><nlm:aff id="A7">Division of Pediatric Urology, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><affiliation><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, California</nlm:aff></affiliation></author><author><name sortKey="Lenz, Heinz Josef" sort="Lenz, Heinz Josef" uniqKey="Lenz H" first="Heinz-Josef" last="Lenz">Heinz-Josef Lenz</name><affiliation><nlm:aff id="A3">Division of Medical Oncology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author><author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name><affiliation><nlm:aff id="A1">Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</nlm:aff></affiliation></author></analytic><series><title level="j">Angiogenesis</title><idno type="ISSN">0969-6970</idno><idno type="eISSN">1573-7209</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57<sup>KIP2</sup> by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis <italic>in vivo</italic>. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis <italic>in vitro</italic> and <italic>in vivo</italic> with a therapeutic efficacy in post-surgical lymphedema.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9814575</journal-id><journal-id journal-id-type="pubmed-jr-id">22063</journal-id><journal-id journal-id-type="nlm-ta">Angiogenesis</journal-id><journal-id journal-id-type="iso-abbrev">Angiogenesis</journal-id><journal-title-group><journal-title>Angiogenesis</journal-title></journal-title-group><issn pub-type="ppub">0969-6970</issn><issn pub-type="epub">1573-7209</issn></journal-meta><article-meta><article-id pub-id-type="pmid">22945845</article-id><article-id pub-id-type="pmc">4166493</article-id><article-id pub-id-type="doi">10.1007/s10456-012-9297-6</article-id><article-id pub-id-type="manuscript">NIHMS406338</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Interleukin-8 Can Reduce Post-Surgical Lymphedema Formation by Promoting Lymphatic Vessel Regeneration</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Inho</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Yong Suk</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Chung</surname><given-names>Hee Kyoung</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Dongwon</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ecoiffier</surname><given-names>Tatiana</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Ha Neul</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Kyu Eui</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Sunju</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Eun Kyung</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Maeng</surname><given-names>Yong Sun</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Nam Yun</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ladner</surname><given-names>Robert D.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Petasis</surname><given-names>Nicos A.</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Koh</surname><given-names>Chester J.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Lu</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Lenz</surname><given-names>Heinz-Josef</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Hong</surname><given-names>Young-Kwon</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref><xref rid="FN1" ref-type="author-notes">8</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Surgery, Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California</aff><aff id="A2"><label>2</label>Department of Pathology, University of Southern California, Los Angeles, California</aff><aff id="A3"><label>3</label>Division of Medical Oncology, University of Southern California, Los Angeles, California</aff><aff id="A4"><label>4</label>Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California</aff><aff id="A5"><label>5</label>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, California</aff><aff id="A6"><label>6</label>Department of Chemistry, Dornsife College of Letters, Arts & Sciences, University of Southern California, Los Angeles, California</aff><aff id="A7"><label>7</label>Division of Pediatric Urology, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California</aff><author-notes><corresp id="FN1"><label>8</label>Correspondence should be addressed to: Young-Kwon Hong, Ph.D., Departments of Surgery, and of Biochemistry and Molecular Biology, University of Southern California, Norris Comprehensive Cancer Center, 1450 Biggy St. NRT6501, Mail Code 9601, Los Angeles, CA 90033, Tel: 323-442-7825, FAX: 323-442-7844, <email>young.hong@usc.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>2</day><month>9</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>04</day><month>9</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>1</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>9</month><year>2014</year></pub-date><volume>16</volume><issue>1</issue><fpage>29</fpage><lpage>44</lpage><pmc-comment>elocation-id from pubmed: 10.1007/s10456-012-9297-6</pmc-comment>
<abstract><p id="P1">Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57<sup>KIP2</sup> by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis <italic>in vivo</italic>. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis <italic>in vitro</italic> and <italic>in vivo</italic> with a therapeutic efficacy in post-surgical lymphedema.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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