Abnormal basement membrane in tumors induced by rat colon cancer cells

Abstract

Background/Aims : Colonic mucosa basement membrane results from a cooperation between epithelial cells and pericryptal fibroblasts characterized as myofibroblasts. This cooperation may be abnormal in colorectal carcinoma resulting in basement membrane alteration. Methods : Basement membrane composition and myofibroblast distribution were studied in normal rat colon and two colon carcinoma models by immunohistochemistry. Colon cancer cells and tumor-associated myofibroblasts were also studied for their capacity to deposit three basement membrane components (laminin, heparan sulfate proteoglycan, and type IV collagen) in vitro. Results : A continuous, type IV collagen-containing basement membrane, such as that observed in normal colon, was found only in the most differentiated tumor model and was restricted to the areas in which myofibroblasts were closely apposed to carcinoma cells. In other areas of this tumor and in the poorly differentiated tumor model, myofibroblasts dissociated from the epithelial cells and the basement membrane was devoid of type IV collagen. In vitro, carcinoma cells deposited laminin and heparan sulfate proteoglycan but not type IV collagen. Tumor-associated myofibroblasts deposited type IV collagen only in the presence of tumor cell extracellular matrix or laminin coating. Conclusions : The colon cancer basement membrane defect in type IV collagen may result from a physical disruption in the association between epithelial cancer cells and myofibroblasts.