Analysis of metastatic tumor cells has revealed expression of factors promoting tissue invasion. Which of the following is/are among such factors?

a. Collagenase

b. Plasminogen activator

Evidence for the involvement of tissue-degradative enzymes in neoplastic invasion is convincing. The production and activation of specific tissue-destructive enzymes such as lysosomal hydrolases and collagenases has been documented in tumor invasion. Destruction of host tissue by hydrolytic enzymes, aided by pressure atrophy and the occlusion of blood and lymph vessels by an expanding tumor mass, facilitates infiltration of neoplastic tissue. Histologic examination of tissues obtained from sites of tumor invasion displays considerable variation in the degree of tissue damage, and many human and animal malignant neoplasms express higher levels of lytic enzymes than benign tumors or corresponding normal tissues. Lysosomal catheptic activities are elevated within some tumor tissues, and increased production of cathepsin B in breast carcinomas has been observed compared with that in normal or benign tissue. Enhanced production and secretion of the serine protease plasminogen activator has been associated with the neoplastic transformation of a variety of cell types.

Both intravasation and extravasion are pivotal in hematogenous, systemic metastasis. In either instance, the tumor cells are confronted with a barrier significantly comprised of type IV collagen. Type IV collagen is a major structural protein of basement membranes between parenchymal cells and the connective tissue on which cells rest. A strong correlation exists between the ability of murine tumor cells to produce spontaneous metastases and their ability to produce increased levels of collagenase IV. Tumor cells that invade blood vessels or leave capillaries of distant organs in which they have lodged must penetrate the basement membrane. Dissolution of the basement membrane, suggestive of enzymatic action, has been observed in areas adjacent to arrested tumor cells.