[Role of connective tissue in the tumor-host relationship]

In the embryo, both differentiation and temporospatial organization are regulated by the mesoderm. Some of these functions are expressed by the connective tissue during wound or organ repair and regeneration. The normal development of the latter depends on the epithelium-mesenchyme interrelationship and the formation of an adequate amount of stroma and a certain type of collagen or proteoglycans. Our hypothesis proposes that cancer is a regenerative process which has failed as a consequence of alterations in the connective tissue. The object of this paper was to investigate whether the connective tissue and the amorphous fundamental substance (SFA) are capable of regulating the proliferation and death of normal and tumor cells and to duplicate the mechanisms involved. The results obtained in vivo, ex-vivo and in vitro experiments indicate that following: 1) SFA exerts a direct and selective cytotoxic effect on tumor cells; 2) SFA reduces the proliferative capacity of normal and tumor cells; 3) both the cytotoxic and antiproliferative effects of SFA are independent of cellular and humoral immune responses but are dependent on the chemical integrity of its component since its denaturalization reduces its antitumoral activity; 4) the tumor cells modulate the regulatory effects of SFA through endocellular enzymes liberated by cell death induced by the cytotoxic action of SFA itself. These results suggest that in the absence of the inhibitory effect of SFA, the tumor cells which remain viable con now proliferate actively due to enzyme stimulation. In conclusion, the regulatory function of the connective tissue on the proliferation and viability of tumor cells would depend on the molecular constitution of SFA.