Melanoma presenting as circulating tumor cells associated with failed angiogenesis

The ability of cancer cells to promote angiogenesis has been associated with a transition from a micrometastatic phenotype to a state in which large solid metastases can form. We describe a case of metastatic melanoma that presented with large numbers of circulating tumor cells and tissue infiltration without large solid metastases. Immunohistochemistry and reverse transcriptase-PCR was used to study the expression of melanoma tumor markers in circulating tumor cells. A tumor cell line was established from the patient and analyzed for adhesion molecule expression, expression of vascular endothelial growth factor, and the ability to inhibit solid tumor formation by other melanoma cells implanted as a xenograft. Examination of the circulating tumor cells confirmed they were of melanoma origin. Analysis of the tumor cell line obtained from this patient demonstrated intact expression of alpha and beta integrins but poor production of vascular endothelial growth factor, and also the ability to inhibit solid tumor formation of third-party melanoma tumors, suggesting a strong antiangiogenic activity. Our results indicate that lethal metastatic melanoma can occur even if tumor angiogenesis is defective, an observation that has implications for potential limits of antiangiogenic therapies.