Bustuoabad O D, di Gianni P D, Genovese J A, Falcó R, Franco M, Ruggiero R A
División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Medicina (B Aires). 1996;56 Suppl 1:25-31.
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.
在胚胎中,分化和时空组织均由中胚层调节。其中一些功能在伤口或器官修复与再生过程中由结缔组织表达。后者的正常发育取决于上皮-间充质相互关系以及适量基质和特定类型胶原蛋白或蛋白聚糖的形成。我们的假设提出,癌症是一种由于结缔组织改变而失败的再生过程。本文的目的是研究结缔组织和无定形基质(SFA)是否能够调节正常细胞和肿瘤细胞的增殖与死亡,并复制其中涉及的机制。体内、体外和离体实验获得的结果表明:1)SFA对肿瘤细胞具有直接和选择性细胞毒性作用;2)SFA降低正常细胞和肿瘤细胞的增殖能力;3)SFA的细胞毒性和抗增殖作用均独立于细胞和体液免疫反应,但取决于其成分的化学完整性,因为其变性会降低其抗肿瘤活性;4)肿瘤细胞通过SFA自身细胞毒性作用诱导细胞死亡释放的细胞内酶来调节SFA的调节作用。这些结果表明,在缺乏SFA抑制作用的情况下,存活下来的肿瘤细胞现在会因酶的刺激而积极增殖。总之,结缔组织对肿瘤细胞增殖和活力的调节功能将取决于SFA的分子组成。