Type XV collagen in human colonic adenocarcinomas has a different distribution than other basement membrane zone proteins

In situ carcinomas must penetrate their own basement membrane to be classif ied as invasive, and subsequently infiltrate surrounding connective tissue and cross vascular basement membranes to metastasize hematogenously. Accord ingly, in many studies, integral basement membrane components, including ty pe IV collagen, laminin, and heparan sulfate proteoglycan, have been locali zed in a spectrum of tumors to gain insight into their role in neoplasia. A number of recently identified extracellular matrix molecules and isoforms of the aforementioned proteins have been localized to the basement mem bran e zone, illustrating another level of biochemical heterogeneity in these st ructures. As the complexity of these matrices becomes more apparent, their roles in maintaining homeostasis and in tumor biology falls into question. Of the new group of collagens localized to the basement membrane zone, type XV was the first to be characterized (Cell Tissue Res, 286:493-505, 1996). This nonfibrillar collagen has a nearly ubiquitous distribution in normal human tissues via a strong association with basement membrane zones, sugges ting that it functions to adhere basement membrane to the underlying stroma . To begin investigation of this protein in malignant tumors, we have local ized type XV in human colonic adenocarcinomas and compared its distribution with that of type IV collagen and laminin. Collagens XV and IV and laminin were found in all normal and colonic epithelial, muscle, fat, neural, and vascular basement membrane zones, as shown previously. In moderately differ entiated, invasive adenocarcinomas, laminin and type IV collagen were somet imes observed as continuous, linear deposits around some of the malignant g lands, but more often they were seen in either discontinuous deposits or we re completely absent. In contrast, type XV collagen was characterized as vi rtually absent from the basement membrane zones of malignant glandular elem ents in moderately differentiated tumors. Nevertheless there were also simi larities; all 3 proteins were usually present in the stroma and adjacent va scular basement membrane zones surrounding invasive glands. The loss of typ e XV collagen from these malignant epithelial basement membrane zones and i ts increased interstitial expression suggests a role for this protein in th e invasive process and the possibility that it may provide a sensitive indi cator of tumor invasion. Copyright (C) 2000 by W.B. Saunders Company.