Analysis of metastasis or morphology related genes in gastrolintestinal carcinoma

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We have used the technique of subtractive complementary DNA(cDNA)cloning to dtermine potential new markers for human gastrointestinal carcinomas. By generating subtraction cDNA libraries from human colon cancer tissue minus that from normal colonic mucosa or hepatocellular carcinoma minus norma liver, we demonstrated that the messenger RNA(mRNA)of ribosomal phosphoprotein and that ofprothymosin-alpha were overexpressed in human colorecatal carcinomatous tissue compared to that from adjacent normal colon mucosa. Conversely, we also demostrated that the mRNA of carbonic anhydrase I was overexpressed in tissue from normal colon mucosa compared to that from colorectal carcinomas.We have recently generated a subtracted cDNA libray from human gastric cancer tissue minus that from normal gastric mucosa from the same patient. One of the overexpressed clones showed 96% identity with matrix metalloproteinase-7(MMP-7).MMP-7 is one of the family members of the matrix-degarding metalloproteinases(MMPs)that may play an important role in invasion and metastasis of cancer cells.We examined the expression of MMP-7 mRNA in different stages of human colorectal carcinomas.The mRNA signal was greater in the colorectal carcinoma that in paired adjacent normal colonic or rectal mucosa in 39 of 47 cases. The expression of MMP-7 mRNA in tumor tissues increased with increasing Dukes'stage(p<0,05).The MMP-7 mRNA expression was greatest in the matastatic liver lesions. The findings imply that 1)MMP-7 mRNA is overexpressed in human colorectal carcinomas, and2)MMP-7 may prove useful as a marker of biological aggressiveness.