[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.