Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma
Identifieur interne : 000075 ( France/Analysis ); précédent : 000074; suivant : 000076Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma
Auteurs : Yeo Kim Pin [Singapour] ; Karen Khoo [Singapour] ; Muly Tham [Singapour] ; Tan Karwai [Singapour] ; Thiam Chung Hwee [Singapour] ; Anne-Laure Puaux [Singapour] ; Meow Ling Cindy Phua [Singapour] ; Masashi Kato [Japon] ; Veronique Angeli [Singapour] ; Jean-Pierre Abastado [Singapour, France]Source :
- Oncotarget [ 1949-2553 ] ; 2015.
Abstract
Resection of infiltrated tumor-draining lymph nodes (TDLNs) is a standard practice for the treatment of several cancers including breast cancer and melanoma. However, many randomized prospective trials have failed to show convincing clinical benefits associated with LN removal and the role of TDLNs in cancer dissemination is poorly understood. Here, we found in a well-characterized spontaneous mouse model of uveal melanoma that the growth of the primary tumor was accompanied by increased lymphangiogenesis and cancer cell colonization in the LNs draining the eyes. But, unexpectedly, early resection of the TDLNs increased the growth of the primary tumor and associated blood vessels as well as promoted cancer cell survival and dissemination. These effects were accompanied by increased tumor cell proliferation and expression of phosphorylated AKT. Topical application of a broad anti-inflammatory agent, Tobradex, or an oral treatment with cyclooxygenase-2 specific inhibitor, Celecoxib, reversed tumor progression observed after complete lymphadenectomy. Our study confirms the importance of tumor homeostasis in cancer progression by showing the enhancing effects of TDLN removal on tumor growth and cancer cell dissemination, and suggests that TDLN resection may only be beneficial if used in combination with anti-inflammatory drugs such as Tobradex and Celecoxib.
Url:
PubMed: 26575174
PubMed Central: 4792593
Affiliations:
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Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea> Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Abastado, Jean Pierre" sort="Abastado, Jean Pierre" uniqKey="Abastado J" first="Jean-Pierre" last="Abastado">Jean-Pierre Abastado</name><affiliation wicri:level="1"><nlm:aff id="A2"> Singapore Immunology Network, BMSI, A-STAR, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea> Singapore Immunology Network, BMSI, A-STAR</wicri:regionArea><wicri:noRegion>A-STAR</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A5"> Present address: Institut de Recherches Internationales Servier, Suresnes Cedex, 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However, many randomized prospective trials have failed to show convincing clinical benefits associated with LN removal and the role of TDLNs in cancer dissemination is poorly understood. Here, we found in a well-characterized spontaneous mouse model of uveal melanoma that the growth of the primary tumor was accompanied by increased lymphangiogenesis and cancer cell colonization in the LNs draining the eyes. But, unexpectedly, early resection of the TDLNs increased the growth of the primary tumor and associated blood vessels as well as promoted cancer cell survival and dissemination. These effects were accompanied by increased tumor cell proliferation and expression of phosphorylated AKT. Topical application of a broad anti-inflammatory agent, Tobradex, or an oral treatment with cyclooxygenase-2 specific inhibitor, Celecoxib, reversed tumor progression observed after complete lymphadenectomy. Our study confirms the importance of tumor homeostasis in cancer progression by showing the enhancing effects of TDLN removal on tumor growth and cancer cell dissemination, and suggests that TDLN resection may only be beneficial if used in combination with anti-inflammatory drugs such as Tobradex and Celecoxib.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Schreiber, Rd" uniqKey="Schreiber R">RD Schreiber</name></author><author><name sortKey="Old, Lj" uniqKey="Old L">LJ Old</name></author><author><name sortKey="Smyth, Mj" uniqKey="Smyth M">MJ Smyth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Angeli, V" uniqKey="Angeli V">V Angeli</name></author><author><name sortKey="Randolph, Gj" uniqKey="Randolph G">GJ Randolph</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lim, Hy" uniqKey="Lim H">HY Lim</name></author><author><name sortKey="Thiam, Ch" uniqKey="Thiam 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sortKey="Yoshioka, I" uniqKey="Yoshioka I">I Yoshioka</name></author><author><name sortKey="Ohashi, Y" uniqKey="Ohashi Y">Y Ohashi</name></author><author><name sortKey="Matsuo, M" uniqKey="Matsuo M">M Matsuo</name></author><author><name sortKey="Harimaya, Y" uniqKey="Harimaya Y">Y Harimaya</name></author><author><name sortKey="Tsukada, K" uniqKey="Tsukada K">K Tsukada</name></author><author><name sortKey="Saiki, I" uniqKey="Saiki I">I Saiki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forget, P" uniqKey="Forget P">P Forget</name></author><author><name sortKey="Vandenhende, J" uniqKey="Vandenhende J">J Vandenhende</name></author><author><name sortKey="Berliere, M" uniqKey="Berliere M">M Berliere</name></author><author><name sortKey="Machiels, Jp" uniqKey="Machiels J">JP Machiels</name></author><author><name sortKey="Nussbaum, B" uniqKey="Nussbaum B">B Nussbaum</name></author><author><name sortKey="Legrand, C" uniqKey="Legrand C">C Legrand</name></author><author><name sortKey="De Kock, M" uniqKey="De Kock M">M De Kock</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li><li>Japon</li><li>Singapour</li></country><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Pin, Yeo Kim" sort="Pin, Yeo Kim" uniqKey="Pin Y" first="Yeo Kim" last="Pin">Yeo Kim Pin</name></noRegion><name sortKey="Abastado, Jean Pierre" sort="Abastado, Jean Pierre" uniqKey="Abastado J" first="Jean-Pierre" last="Abastado">Jean-Pierre Abastado</name><name sortKey="Angeli, Veronique" sort="Angeli, Veronique" uniqKey="Angeli V" first="Veronique" last="Angeli">Veronique Angeli</name><name sortKey="Cindy Phua, Meow Ling" sort="Cindy Phua, Meow Ling" uniqKey="Cindy Phua M" first="Meow Ling" last="Cindy Phua">Meow Ling Cindy Phua</name><name sortKey="Hwee, Thiam Chung" sort="Hwee, Thiam Chung" uniqKey="Hwee T" first="Thiam Chung" last="Hwee">Thiam Chung Hwee</name><name sortKey="Karwai, Tan" sort="Karwai, Tan" uniqKey="Karwai T" first="Tan" last="Karwai">Tan Karwai</name><name sortKey="Karwai, Tan" sort="Karwai, Tan" uniqKey="Karwai T" first="Tan" last="Karwai">Tan Karwai</name><name sortKey="Khoo, Karen" sort="Khoo, Karen" uniqKey="Khoo K" first="Karen" last="Khoo">Karen Khoo</name><name sortKey="Puaux, Anne Laure" sort="Puaux, Anne Laure" uniqKey="Puaux A" first="Anne-Laure" last="Puaux">Anne-Laure Puaux</name><name sortKey="Tham, Muly" sort="Tham, Muly" uniqKey="Tham M" first="Muly" last="Tham">Muly Tham</name></country><country name="Japon"><noRegion><name sortKey="Kato, Masashi" sort="Kato, Masashi" uniqKey="Kato M" first="Masashi" last="Kato">Masashi Kato</name></noRegion></country><country name="France"><noRegion><name sortKey="Abastado, Jean Pierre" sort="Abastado, Jean Pierre" uniqKey="Abastado J" first="Jean-Pierre" last="Abastado">Jean-Pierre Abastado</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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