Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.

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.