| Co-Investigator(Kenkyū-buntansha) |
NAKAHASHI Yoshitsugu Kansai Medical University, School of medicine, Assistant professor, 医学部, 助手 (70247930)
MATSUZAKI Koichi Kansai Medical University, School of medicine, Assistant professor, 医学部, 講師 (70278638)
SEKI Toshihito Kansai Medical University, School of medicine, Associate professor, 医学部, 助教授 (70163087)
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| Research Abstract |
The progression of a tumor cells from one of benign delimited proliferation to invasive and metastatic growth is the major cause of poor clinical outcome in the patients with cancer. During the process of invasion and metastasis, cancer cells are known to interact with extracellular matrices (ECM), endothelial cells, platelets and other organ-specific structure. The integrins are heterodimeric molecules which mediate cell-ECM and cell-cell interactions, and are likely to be important for cancer cell survival and dissemination.
Recent findings from our laboratory have indicated that the types and levels of integrins in human hepatocellular carcinoma (HCC) cell lines are required during the following steps in the generation of distant metastases : a) angiogenesis ; b) detachment from the primary site ; c) migration ; d) intra- and extra-vasation (adhesion to vascular endothelium), and e) proliferation. We next investigated the expression of integrins in the specimens obtained from the pat
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ients with HCC, and found that notable changes in several integrin subunits occurred during tumor progression and invasion. These changes included increased or decreased expression, or changes in distribution from a polarized to a dispersed pattern, and were well correlated with malignant phenotypes of human HCC such as poor differentiation, size of tumor, absence of capsule, invasion to portal veins, and distant metastasis. Alterations in the integrin expression are useful as cancer invasion markers for prognostic and for diagnostic purpose.
Once invading cancer cells have gained access to the circulation, adhesion to the endothelia and other tissue components facilitates the establishment of tumor colonies at distant sites. Angiogenic endothelial cells in tumor vessels depend on the alpha v family of integrins for survival. Interfering with cancer cell attachment with integrin-binding cyclic peptides, and inhibiting angiogenesis with compounds that block the activity of alpha v subunits have been shown to be an effective anti-metastatic strategy. Ongoing efforts to develop specific pharmacological agonists and antagonists for integrins hold great promise in clinical medicine. Less
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