Studies on prediction and inhibition for metastasis from carcinomas of the digestive tract

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We have established the method of in vitro quantitative assay (invasion MTT assay) for studying invasive potentiality and metastatic behavior of the cancer cells using carcinomas of the digestive tract. The invasive potentiality to the basement membrane was estimated as percent invasion, that is the occurrence of the seeded cells in the cell chamber which penetrate through the basement membrane (percentage of the invaded cells to the seeded cells). The percent invasion values of tumors with liver metastasis were significantly higher than those of tumors without metastasis (p<0.001), although, it did not correlate with both type IV collagenase activity and cell capability of the adhesion, chemotaxis, and proliferation. The type IV collagenase activity was significantly higher in patients with liver metastasis, suggesting it has an important role to accelerate the liver metastasis.Clinicopathological parameters in 906 patients with carcinomas of the digestive tract were studied to know prediction capability for the liver metastasis using univariate analysis, resulting that vessel invasion and lymph node metastasis were the significant parameters. Using those parameters for the prediction, its specificity was more than 90% but sensitivity was less than 20%. Whereas, the percent invasion was measured using 30 tumors xenografted in nude mice obtained from the 906 patients. Its specificity for the prediction was 90% and sensitivity was 70%. An assessment of invasive potentiality to the basement membrane using the invasion MTT assay seemed to be useful method for predicting the liver metastasis form carcinomas of the digestive tract.