| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, >100years ago, formulated his seed and soil hypothesis, i.e., the cells from a given tumor would "seed" only favorable "soil" offered by certain organs. The hypothesis implies that cancer cells must find a suitable "soil" in a target organ-i.e., one that supports colonization-for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behaviro of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor
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behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors affixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.
2.We have investigated the expression of the integrin beta1 subunit in 51 colorectal cancer tissues using immunoblotting and have determined the relationship between expression and clinical stage. In comparison with normal mucosa the pre-beta-subunit (the precursor of beta1-subunit) was increased in 15 cases and decreased in two cases, and expression of the beta1-subunit was decreased in two cases. These alterations of expression of the beta1-subunit were significantly correlated with lymph node metastasis and depth of invasion (P<0.01). These results suggest that integrin plays an important role in the invasion and metastasis of colorectal cancer. Less
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