Yamamoto H, Itoh F, Hinoda Y, Imai K
First Department of Internal Medicine, Sapporo Medical University, Japan.
Cancer Res. 1996 Aug 1;56(15):3605-9.
Alterations in several classes of adhesion molecules 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 a 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. To further study the biological significance of CAR expression in colon cancer cells, a CAR expression vector was introduced into HT-29 cells, in which CAR is not expressed. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. In spite of similar growth properties with the controls, CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated CAR expression in 30 surgical specimen pairs of human colorectal cancer and adjacent noncancerous tissue using semiquantitative reverse transcription-PCR. 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 metastasis than in those without it (P < 0.01) and in patients with distant metastasis than in those without it (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.
几类黏附分子的改变与结直肠癌的进展有关。细胞黏附调节因子（CAR）已被确定为整合素依赖性细胞黏附的调节分子。我们探讨了CAR基因在结直肠癌中的可能作用。逆转录聚合酶链反应显示，正常结肠细胞中可检测到CAR表达，而在13个人结肠癌细胞系中的6个（46.2%）中，其表达降低或无法检测到。为了进一步研究CAR在结肠癌细胞中表达的生物学意义，将CAR表达载体导入不表达CAR的HT-29细胞中。CAR的导入上调了HT-29细胞与细胞外基质成分的黏附。尽管与对照相比生长特性相似，但转染CAR的HT-29细胞在裸鼠中的自发转移潜能显著降低。为了确定这些实验结果是否与实际人类肿瘤相关，我们使用半定量逆转录聚合酶链反应研究了30对人结直肠癌手术标本及其相邻非癌组织中的CAR表达。在30例病例中的14例（46.7%）中，癌组织中的CAR表达不到配对非癌组织的十分之一。有淋巴结转移的患者与无淋巴结转移的患者相比，CAR表达的肿瘤/正常组织比值显著更低（P<0.01），有远处转移的患者与无远处转移的患者相比也是如此（P<0.05）。在更晚期的杜克分期肿瘤中，CAR表达显著更低（P<0.05）。我们的结果表明，CAR表达下调可能在结直肠癌的进展和转移中起重要作用。
