Melanoma: Molecular Signalling at the Tumour-Vessel Interface

Abstract

Abstract: : Purpose:To determine if an expanding tumour and its simultaneously expanding vasculature exchange molecular signals for sustained growth; and to determine if these signals are derived exclusively from the tumour cells or from the vasculature. We hope to identify uniquely expressed therapeutic targets. Methods:<Using a murine xenograft model of human melanoma (M21), angiogenesis-related mRNA and protein expression were assessed using confocal immunohistochemistry (IHC), gel zymography, in situ zymography (ISZ), and species-specific real-time quantitative PCR (rtqPCR). Genes assessed include CD31, endoglin, collagen IV, integrins av, b3, b5, mmp-2, mmp-9 and EMMPRIN. Results:IHC confirms that intra-tumoural vessels are derived from the murine host, and that when compared aginst normal vessels, they display abnormal morphology, collagen IV and mmp-9 distribution. ISZ indicates that proteases are active along the vessels. Species-specific rtqPCR indicates that while some genes (eg integrin av) are expressed by human tumour and murine host, some genes (eg mmp-9) are expressed exclusively by the host. Conclusion:These data suggest that the tumour-vessel interface is actively being remodeled, and that sustained, co-ordinated growth of a tumour and its vessels requires on-going, bi-directional signaling. Targeted disruption of this molecular dialogue is the ultimate goal of this work.

Keywords: 464 melanoma • 496 oncology