P-cadherin expression reduces melanoma growth, invasion, and responsiveness to growth factors in nude mice

Abstract

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 (1621 mm ± 107 vs. 329 mm ± 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 (3896 mm ± 64 vs. 1621 mm ± 107) in contrast to BLM P-cad (417 mm ± 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.