MECHANISMS AND INHITION OF THE INVASION OF MALIGNANT BONE AND SOFT TISSUE TUMORS THROUGH BASEMENT MEMBRANES

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Tumor invasion of the basement membranes is a crucial step in the complex multistage process which leads to the formation of metastasis. Tumor cells cross the basement membranes as they initially invade vascular beds during dissemination, and then they penetrate their target tissue. The treatment of human fibrosarcoma cells HT1080 with cAMP analogues and chorela toxin that increase the intra-cellular cAMP concentrations induces the expression of Timp-1 and Timp-2 both at the mRNA and the protein levels. This induction of Timps correlated well with type IV collagenolytic activity, invasiveness and metastatic potential of HT1080 cells.We developed a quantitative assay for assessing in vivo tumor angiogenesis using basement membrane extracts (Matrigel). Nude mice are injected s.c. with liquid Matrigel mixed with HT1080 cells. Since Matrigel forms a solid gel rapidly at body temperature, the gel containing tumor cells can be removed immediately, and the processed for histological studies. Tumor angiogenesis was monitored quantitatively by measuring both the number and total area of neovessels present in the gels using an image analyzer.