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.
[Show abstract][Hide abstract] ABSTRACT: The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.
Thandokuhle Khumalo, Eloise Ferreira, Katarina Jovanovic, Rob B Veale, Stefan F T Weiss
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