The basement membrane and its involvement in carcinoma cell invasion

During the development of invasive cancer, carcinoma cells have to penetrate the extracellular matrix including the basement membrane (BM). This is a usually continuous layer composed of a dense meshwork of collagens, glycoproteins and proteoglycans. It normally underlies epithelia and lacks any pores large enough to allow epithelial cells to pass through them. In consequence, the invasion of carcinoma cells through the BM must be either an active process effected by the carcinoma cells themselves or is mediated by structural alterations of the BM occurring during carcinogenesis and cancer progression. It was supposed by many authors that invading and metastasizing carcinoma cells are able to degrade actively the continuous, uninterrupted BM by secreting type IV collagenase and other proteolytic enzymes. Although there is a wealth of experimental evidence which fits the concept that the active degradation of the BM is an essential requirement for carcinoma cell invasion and metastasis, certain data do not agree with this hypothesis. Thus, it is still doubtful whether active lysis of the BM by carcinoma cells is actually a prerequisite for invasion and metastasis or whether there are alternative and/or additional mechanisms favoring the invasion of carcinoma cells.