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Title
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P-cadherin expression reduces melanoma growth, invasion, and responsiveness to growth factors in nude mice
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Author
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Abstract
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| The prognostic discrepancy between localized melanoma and metastatic disease demands a better understanding of melanoma progression. The role of E-cadherin and N-cadherin in melanoma has been widely studied; however, the function of P-cadherin remains to be elucidated. We wanted to assess the effects of P-cadherin overexpression in BLM melanoma cells with regard to xenograft growth, invasion, and survival of mice in our model to mimic micrometastatic spread. Swiss nu/nu mice were subcutaneously injected with control (BLM LIE) and P-cadherin overexpressing (BLM P-cad) melanoma cells alone and in combination with myofibroblasts, and intracardially injected with BLM LIE and BLM P-cad cells. Tumor volumes and survival of mice were assessed and analyzed. In-vitro assays were used to further investigate the influence, and identify the target receptors of growth factors secreted by myofibroblasts in melanoma cells. In-vivo experiments point out that P-cadherin reduces xenograft growth (1621mm(3) +/- 107 vs. 329mm(3) +/- 71) and invasion, and prolongs overall survival (34.1 +/- 0.84 vs. 51.1 +/- 1.8 days) of mice in our model to mimic micrometastatic spread. Coinjection with myofibroblasts resulted in increased tumor growth in BLM LIE (3896mm(3) +/- 64 vs. 1621mm(3) +/- 107) in contrast to BLM P-cad (417mm(3) +/- 47 vs. 329 +/- 71). P-cadherin reduces melanoma growth and invasion, prolongs the survival of mice intracardially injected, and induces a state of decreased responsiveness to myofibroblast-derived growth factors. Therefore, P-cadherin can be considered as a potential therapeutic target in the treatment of melanoma. European Journal of Cancer Prevention 20:207-216 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. |
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Language
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English
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Source (journal)
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European journal of cancer prevention. - Oxford, 1991, currens
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Publication
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Oxford
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2011
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ISSN
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0959-8278
[print]
1473-5709
[online]
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DOI
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10.1097/CEJ.0B013E3283429E8B
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Volume/pages
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20
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(2011)
, p. 207-216
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ISI
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000288892700009
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Pubmed ID
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21445019
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Full text (Publisher's DOI)
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