STROMAL REACTION IN CANCER-TISSUE - PATHOPHYSIOLOGIC SIGNIFICANCE OF THE EXPRESSION OF MATRIX-DEGRADING ENZYMES IN RELATION TO MATRIX TURNOVER AND IMMUNE INFLAMMATORY REACTIONS/

Cancers are characterized by invasive growth and distant metastasis. C ancer cells not only destroy the pre-existing extracellular matrix, bu t cancer invasion per se usually induces new matrix formation by activ ation of stromal cells; that is, desmoplastic reaction. This process i ncludes both matrix production and degradation; that is, the remodelin g process. The similarity between desmoplastic reactions in cancer str oma and the wound healing process has already been pointed out, and it has been well documented that matrix-degrading processes are actively involved in the wound healing process. A recent study revealed that m ost matrix-degrading enzymes, generally considered to be one of the ma in mechanisms of cancer invasion and metastasis, are originated from s tromal cells. Based on these preconditions, the present review postula tes that the abundant expression of matrix-degrading enzymes by fibrob lasts, coupled with the abundant expression of type I procollagen, is involved in the matrix remodeling processes occurring in cancer stroma ; that is, the mechanism similar to the wound healing process. Next, m acrophages distributed along the invasive margin are known to express matrix-degrading enzymes/factors. Data from past studies of colon carc inoma indicate that the tissue expression of matrix metalloproteinase- 9 and urokinase-type plasminogen activator receptor is inversely assoc iated with simultaneous liver metastasis and infiltrating growth patte rn. Previous clinicopathologic data have indicated that immune/inflamm atory cells are one of the factors for a favorable prognosis. This sug gests that the expression of matrix-degrading enzymes/factors by these host cells may be involved in host immune/inflammatory reactions, and that the net function of these cells can be defensive towards the hos t. Data from past studies of colon carcinoma on the expression of the intercellular adhesion molecule-1 suggest that the interaction between macrophages, lymphocytes, and the phenotypes of venules distributed a long the invasive margin, further support the pro-inflammatory milieu there. Therefore, the matrix degradation process in cancer tissue is m ultifunctional: besides the involvement in cancer invasion and metasta sis, the matrix degradation process is also involved in the tissue rem odeling process and in the immune/inflammatory reaction occurring in t he stroma.