Vascular endothelial growth factor is an autocrine growth factor for cardiac myxoma cells

Abstract

Background: Cardiac myxomas are generally considered benign, but malignant tumors have been reported. Vascular endothelial growth factor (VEGF), an angiogenic factor, plays a role in the growth, progression, and metastasis of solid tumors and it has been reported that VEGF expression is upregulated in cardiac myxomas that have a high microvessel density. The purpose of this study was to determine whether cardiac myxoma cells possess a VEGF-autocrine system that regulates tumor growth. Methods and Results: Immunohistochemical analyses revealed the presence of VEGF and its receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1), in the cytoplasm of tumor cells from 18 of 18 myxoma tissue specimens examined. Two different myxoma cell lines were established and constitutively secreted large amounts of VEGF as determined by enzyme-linked immunosorbent assay. The expression of VEGF, VEGFR-1, and VEGFR-2 mRNA was detected in both cell lines by reverse-transcriptase polymerase chain reaction. Myxoma cell proliferation, as determined by thymidine incorporation, was enhanced by the addition of VEGF in a dose-dependent manner, and cell proliferation was inhibited in a dose-dependent manner by the addition of a neutralizing VEGF antibody. Conclusions: These results indicate that cardiac myxoma cells possess a VEGF-autocrine system, which could contribute to the malignant potential of histologically benign myxomas through direct stimulation of tumor cell growth as well as through induction of angiogenesis.