Research Abstract |
It is very important to elucidate the mechanism of interection between cancer cells and extracellular matrix components for understanding the cancer metastasis and designing the method useful for its prevention. The adhesion of cancer cells to the endothelial basement. membrane is especially important in the metastatic process, and the inhibition of this step would be effective to inhibit cancer metastasis. During search for the compounds which prevent the adhesion of cancer cells to the basement membrane components, fibronectin and collagen, we have found that the extracts from certain mushrooms can inhibit the adhesion of mouse Lewis lung carcinoma cells to type IV collagen. In the present study, we examined the characteristics of the 23kDa type IV collagen-binding protein (HM-23) which was isolated from mushroom Hypsizigus marmoreus by affinity chromatography. As a result, we found that HM-23 inhibited the adhesion of 3LL cells to type IV collagen. The partial amino acid sequences d
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etermined has revealed that HM-23 has homology to fibromodulin, which regulates the formation of collagen fibrils, and that HM-23 is hitherto unknown protein. Cyanogen bromide degradation of HM-23 resulted in generation of two poly-peptides with about 110kDA,suggesting that methionine is present at the center of the molecule. The amino acid sequencing of these polypeptides suggested that this methionine residue is the one contained in one of the three determined sequences. Anti-HM-23 antibodies were used to examine the interaction between HM-23 and extracellular matrix proteins by application of the enzyme-linked immunoadsorbent assay. The results have indicated that HM-23 binds to type I collagen, type IV collagen and gelatin, and to fibronectin weakly, but not to laminin at all. In addition to this mushroom protein exhibiting interaction with animal extracellular matrix proteins, we have also found that rice bran contains fibronectin-binding proteins. These findings on the interaction between non-animal proteins and animal extracellular matrix proteins would open a wide range of biological and cell biological interests which will lead to provide the answers for the problems inculuding cancer metastasis. Less
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