CHANGES IN COLLAGEN METABOLISM IN PROSTATE CANCER: A HOST RESPONSE THAT MAY ALTER PROGRESSION

Abstract

The interaction of cancer cells and the extracellular matrix is essential for cancer progression. However, little is known about the influence of cancer on the metabolism of collagen, which is the major constituent of the extracellular matrix. We studied changes in collagen metabolism in prostate cancer with increasing Gleason score and correlated them with clinical parameters and patient survival.Collagen content and clinical parameters in 3 types of prostatic tissue were compared, including the foci of prostatic cancer, unaffected tissue from the same cancerous prostates and prostatic tissue from patients with no evidence of cancer. In addition, to assess collagen metabolism tissue obtained prospectively from 45 patients undergoing prostatic biopsy was assessed for collagen content, the type and extent of collagen cross-linking, serine proteinase, matrix metalloproteinase and the C-terminal propeptide of type I collagen.With increasing Gleason sum of the cancer collagen content at the focus decreased, while that of surrounding unaffected tissue from the same prostate increased to levels significantly above that from controls with no cancer. Markers of collagen synthesis in the prostate biopsy material were significantly increased in the presence of prostate cancer.In prostate cancer there are changes in collagen metabolism not only in the cancer focus but also in nearby histologically benign prostatic tissue. These observed changes are related to the Gleason score of the tumor and may represent a host response. Collagen content in the surrounding unaffected tissue may be a predictor of patient survival.