Modulation of the Extracellular Matrix by Tumor Cell-Fibroblast Interactions

Abstract

Tumor cell invasion and metastasis involve numerous cellular phenomena, e.g., changes in cytoskeletal and cell-surface characteristics, interactions between tumor cells and cells of the vascular and immune systems, and penetration of extracellular matrices. In relation to the last of these phenomena, two major classes of extracellular matrices are traversed by malignant tumor cells during invasion of host tissues, viz., interstitial matrices and basement membranes. It is apparent that successful penetration of extracellular matrices by tumor cells would depend on at least two types of alterations in the structure of these matrices: (1) destruction of preexisting extracellular matrix barriers, and (2) reconstruction of a suitable extracellular environment for cell movement and proliferation. Both of these requirements are, in turn, certain to be multifaceted. However, important in the former would be production of degradative enzymes, such as type I collagenase (Gross et al., 1981; Biswas, 1982a; Woolley, 1982, 1984), type IV collagenase (Liotta et al., 1983; Liotta, 1986), heparanase (Kramer et al., 1982; Nakajima et al., 1983), cathepsin B (Poole et al., 1978;Graf et al., 1981;Sloane et al., 1986), and plasminogen activator (Ossowski and Reich, 1983). Important in the latter is likely to be production of those extracellular macromolecules characteristic of the pericellular milieu of migratory and proliferating cells in embryonic tissues, e.g., hyaluronate (Toole, 1981; Toole et al., 1984) and