PARTICIPATION OF EXTRACELLULAR-MATRIX PROTEINS IN TUMOR HISTOGENESIS IN-VITRO

Using a newly established human endometrial carcinoma cell line, EMAC-5, we have investigated tumor cell growth and histogenesis with relation to extracellular matrices (ECM). EMAC-5 cells in regular culture dishes are epithelial and anaplastic. When transplanted into nude mice, EMAC-5 cells developed tumors consisting of a mixed histology of glandular structures which were fringed with a basement membrane, and solid areas. When provided with an appropriate ECM substratum, EMAC-5 cells in vitro showed morphological differentiation to form cellular cystic spheroids (CCS) composed of polarized monolayer cells having a basement membrane-like lining on the interior basal surface;toward the cavity and microvilli on the outer surface facing to the culture milieu. The entire configuration of CCS was obviously the inside-out reversed form of an endometrial gland, in which the basement membrane was seen along the farther side from the glandular cavity and microvilli were facing directly to the cavity. The CCS-forming activities of ECM proteins were correlated with the responses of the cells to ECM, but the mere adhesiveness or the growth-promoting activity of culture surface was not correlated with the CCS-forming activities. Replating CCS on ECM to which the cells adhere well, generated the outgrowth of anaplastic cells on the culture surface with recovered growth activity. These findings imply that ECM play a significant role in the regulation of the growth and differentiation of endometrial carcinoma cells.