Use of cell culture to identify human precancer.

Abstract

In the United States, colon cancer is the most common form of internal cancer in both sexes. Prevention of the disease depends on early diagnosis of polyps or pre-cancerous lesions. The response of normal human colon fibroblasts ( CRL1459 ) was used to identify individuals with clinical pre-cancer. Their plasma induced transformation associated morphology characterized by the retraction of cellular processes, cell rounding and eventual detachment from the vessel surface. Those plasma samples which induced a transformation associated morphology contained significantly increased levels of protease as shown by casein hydrolysis (Bio-Rad, CA). We are using hyperproteinasemia as a biomarker to identify individuals with polyps who have hereditary adenomatosis of the colon and rectum (ACR). We are currently evaluating cell cultures versus biochemical assays as a means for early detection of precancerous tumors in the general population. The findings of a tumor associated protease in clinical precancer, and its effect on cell cultures support our proposal that protease activity promotes tumor progression in ACR and may represent the gene defect in this hereditary disease.