Effects of Titanocene Dichloride on Endothelial Cells in Vitro

Abstract

Endothelium responds to tumor factors by migration and proliferation, which can lead to angiogenesis (Hobson and Denekamp, 1984). Angiogenesis is an essential process for solid tumor growth and metastases and has therefore been considered as a possible target for tumor therapy (Blood and Zetter, 1990). Indeed, it has been shown that inhibition of angiogenesis can inhibit solid tumor growth (Folkman, 1972; Maragoudakis et al., 1990). Extracellular matrix (ECM) is a regulator of the angiogenic process (Adams and Watt, 1993) and, as such, it can be targeted in order to manipulate angiogenesis. We have investigated titanocene dichloride (TD), a novel antitumor agent with remarkably low toxicity in vivo (Kopf-Majer and Kopf, 1986) and strong antiangiogenic properties (Bastaki et al, 1994) for its effects on ECM secretion and deposition by endothelial cells (EC), as a possible mechanism for its antiangiogenic action. An in vitro system was employed, based on microvascular endothelial cells cultured on collagen I in medium with or without tumor-conditioned medium, the production of fibronectin (FN) and laminin (LM), two of the major components of the ECM was then examined in the medium, intracellular phase and subcellular matrix by ELISA.