Gene Products of the Major Histocompatibility Complex Control the Metastatic Phenotype of Tumor Cells

Abstract

To generate metastases, neoplastic cells should be capable of detaching themselves from the local growth, of invading extracellular matrices, of penetrating basement membranes of blood of extravasating while manifesting, in many cases, specific recognition of target organs, and of inducing angiogenesis essential for the growth of metastasis. Since the local tumor cell population was shown to be diverse with respect to the metastatic competence of its individual cells (1), nonmetastatic cells of a metastatic tumor may be impaired with regards to all, a few or any one of the sequential steps culminating in metastatic growth. Recent studies in our laboratories of two metastatic tumors, the 3LL Lewis Lung Carcinoma and the T10 Sarcoma, indicated that metastatic clones and nonmetastatic clones synthesize and secrete similar levels of collagenase IV (2), an enzyme which was previously implicated as part of the enzymatic weaponry for metastatic penetration of basement membranes (3). And although the synthesis of another relevant enzyme, plasminogen activator, was higher in metastatic compared to nonmetastatic clones (4), this did not seem to represent a rate-limiting factor in the initial invasion processes (4).