Extracellular matrix and the patterns of differentiation of human endometrial carcinomas in vitro and in vivo.

Abstract

Adenocarcinomas differ in their ability to form glandular structures, and the mechanism regulating this architectural differentiation is unknown. In the present study, the patterns of differentiation of two human endometrial carcinomas that differed with respect to their ability to form glands in their original host were studied in monolayer and three-dimensional cultures as well as in xenografts in athymic mice. A moderately differentiated adenocarcinoma of human endometrium, EnCa101, transplanted into nude mice formed tumors indistinguishable from the original neoplasm and secreted mucin. A cell line derived from this tumor, ECC-1, formed monolayers on tissue culture substratum and lost the ability to secrete mucin. However, upon culture within Matrigel, the ECC-1 cells formed glandular structures and secreted mucin. Ultrastructural examination revealed morphological polarity, as evident by intraluminal microvilli and characteristic adhesion structures composed of tight, gap, and desmosomal junctions adjacent to the lumen, and secretory activity. Whereas basal lamina was observed in vivo around glandular cells, epithelial cells were not tethered in vitro with this structure. In contrast, the epithelial cells of a poorly differentiated human endometrial adenocarcinoma, AN3, failed to form glands in nude mice or in Matrigel in vitro. These findings illustrate that gland-forming ability is an intrinsic property of well to moderately differentiated adenocarcinoma cells and that only cells with this inherent potential can be induced to form glands in response to appropriate extracellular signals.