J.Jpn. Surg. Soc.. 99(7): 415-418, 1998

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Feature topic

REGULATION OF INTEGRIN FUNCTION IN THE METASTASIS OF COLORECTAL CANCER

Alterations in several classes of adhesion molecule have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored the possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2％) human colon cancer cell lines. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. In 14 of 30 cases (46.7％), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor : normal ratio of CAR expression was significantly lower in patients with lymph node metastases than in those without (p< 0.01) and in patients with distant metastases than in those without (p< 0.05). CAR expression was significantly lower in more advanced Dukes’stage tumors (p< 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.

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