Cytokines and proteases in invasive processes: molecular similarities between inflammation and cancer.
Tumor-derived serine proteinases and metalloproteinases have been associated with invasion and metastasis of cancer cells. Leukocytes, particularly monocytes/macrophages and neutrophils, actively synthesize and store these proteolytic enzymes. The production by tumor cells of chemotactic factors that attract white blood cells raises questions that are important for the basic researcher as well as the clinical scientist. Are the proteinases, which have the capacity to dissolve the extracellular matrix and by this solubilization promote cell migration, the same in tumor cells as in normal cells? Is the production of chemotactic factors by tumor cells a coincident epiphenomenon of the malignant state or a selective way to parasitize the host? Does the early attraction of leukocytes to the tumor site contribute to early host defense against cancer? Does our knowledge about mechanisms of action of cytokines have implications for therapy of the cancer patient? Recent experimental data give hints to the answers to these questions and make it possible to deduce a fundamental model of cytokine mediated proteolysis in tissue remodelling.
Opdenakker
G
G
Rega Institute for Medical Research, Leuven, Belgium.
Van Damme
J
J
D000818:Animals; D002273:Carcinogens; D002630:Chemotactic Factors / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*
D002273:Carcinogens; D002630:Chemotactic Factors; D016207:Cytokines; D010450:Endopeptidases