Tumor invasion and its local regulation

Abstract

Introduction The ability to invade normal tissue which ~ur­ rounds a primary tumor and to subsequently metastasize to distant sites are the distinguishing features of malignant neoplasms. I In order to invade and metastasize, tumor cells must overcome several structural barriers of host tissues. These barriers include parenchymal cells (i.e., epithelium, endothelium), basement membranes (continuous, lamrnellar extracellular matrices to which parenchymal cells are attached), and connective tissue matrices. Invasive tumors arising in epithelia (i.e., urinary bladder epithelium) first penetrate the epithelial basement membrane. Once carcinoma cells have entered and invaded the underlying connective tissue, they gain access to vascular and lymphatic channels (intravasation), Tumor cell entry into the circulation requires the penetration of vascular basement membrane and endothelium. If tumor cells survive passage within vessels, they localize at fertile sites, make their way out of the vessel (extravasation), penetrate the perivascular connective tissue, an~ proliferate to form a metastatic focus (Figure. 1).1:Tumor cell penetration of each of these barriers IS accomplished by altering the physical properties of constituent host tissues in such a way that they allow the migration of cancer cells to deeper zones and that they provide space to house continuously multiplying tumor cell populations. In contrast, the noninvasive cell populations of benign neoplasms are unable to induce such alterations, and some may even isolate themselves from host tissues by a solid connective tissue capsule. The effect of non-invasive cells on the host results only in compression and displacement of surrounding tissue, but these tumor