Melanoma presenting as circulating tumor cells associated with failed angiogenesis

Abstract

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.

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

“…It is well established that a melanoma cell may invade the circulation and survive without clinical evidence of a primary tumour, and so, not infrequently a patient may have metastatic melanoma without a known cutaneous primary site [67,68]. In fact, melanoma can still be lethal even when solid tumours cannot form due to the patient having an inbuilt inability for the tumours to form a vascular supply [4]. In this case the patient developed high levels of cells in the blood and CSF and eventually succumbed to renal failure from tumour lysis syndrome.…”

“…In the United States, CMM is an emerging problem as the incidence has increased more than that of any other cancer over the past two decades. More specifically, in 2005 the American Cancer Society recorded approximately 59,580 new cases and over 7,910 new deaths [3,4].…”

Circulating tumor cells: a new challenge for laboratory medicine

“…Cette aptitude n'a jusqu'à présent été évaluée que par des études indirectes dans les CTC. L'expression du VEGF et de son ARNm a été montrée comme faible dans une lignée cellulaire établie à partir des CTC d'un mélanome métastatique[42]. Une autre étude angiogéniques est retrouvée dans 81 % (pFAK), 73 % (VEGF), 71 % (VEGF2) et 56 % (HIF1-␣) de l'ensemble des CTC des 34 patientes[44].…”