ROLE OF THE CONNECTIVE-TISSUE IN THE TUMO R-HOST RELATIONSHIP

In the embryo, both differentiation and temporospatial organization ar e regulated by the mesoderm. Some of these functions are expressed by the connective tissue during wound or organ repair and regeneration. T he normal development of the latter depends on the epithelium-mesenchy me interrelationship and the formation of an adequate amount of stroma and a certain type of collagen or proteoglycans. Our hypothesis propo ses that cancer is a regenerative process which has failed as a conseq uence of alterations in the connective tissue. The object of this pape r was to investigate whether the connective tissue and the amorphous f undamental substance (SFA) are capable of regulating the proliferation and death of normal and tumor cells and to dilucidate the mechanisms involved. The results obtained in in vivo, ex-vivo and in vitro experi ments indicate the following: 1) SFA exerts a direct and selective cyt otoxic effect on tumor cells; 2) SFA reduces the proliferative capacit y of normal and tumor cells; 3) both the cytotoxic and antiproliferati ve effects of SFA are independent of cellular and humoral immune respo nses but are dependent on the chemical integrity of its components sin ce its denaturalization reduces its antitumoral activity; 4) the tumor cells modulate the regulatory effects of SFA through endocellular enz ymes liberated by cell death induced by the cytotoxic action of SFA it self. These results suggest that in the absence of the inhibitory effe ct of SFA, the tumor cells which remain viable con now proliferate act ively due to enzyme stimulation. In conclusion, the regulatory functio n of the connective tissue on the proliferation and viability of tumor cells would depend on the molecular constitution of SFA.