Levy A T, Cioce V, Sobel M E, Garbisa S, Grigioni W F, Liotta L A, Stetler-Stevenson W G
Tumor Invasion and Metastasis Section, National Cancer Institute Bethesda, Maryland 20892.
Cancer Res. 1991 Jan 1;51(1):439-44.
Proteolytic enzymes, such as type IV collagenase, play an important role in tumor invasion and metastasis. To examine Mr 72,000 type IV collagenase expression in human colon carcinoma, blot hybridization of total RNA from 19 primary colon tumors were performed. These filters were probed with complementary DNA probes encoding the Mr 72,000 type IV collagenase metalloenzyme. The results were expressed as the ratio of the messenger RNA (mRNA) levels in the tumor tissue to that in the adjacent normal mucosa (R). The level of the 3.1-kilobase type IV collagenase mRNA was higher in the primary tumor than in the normal adjacent colonic mucosa in 13 of 18 (72%) cases with a diagnosis of adenocarcinoma. These cases were divided into high expression (R, 4.50 to 29.34) and intermediate expression (R, 2.54 to 3.31) subgroups. Both groups showed statistically significant (P less than 0.05) elevations when compared with the five cases showing the lowest levels of Mr 72,000 type IV collagenase mRNA expression (low expression subgroup; R, 0.96 to 1.48). With this demonstrated elevation of Mr 72,000 type IV collagenase mRNA in colorectal adenocarcinoma we examined concomitant expression at the protein level using immunohistochemical techniques. Immunohistochemical examination of 70 cases of colon tumors, including 30 benign adenomas, using anti-Mr 72,000 type IV collagenase antibodies demonstrated a significant correlation with Duke's classification (P less than 0.001). Our results suggest that enhanced expression of the Mr 72,000 type IV collagenase enzyme may be a marker of human colorectal tumor invasiveness.
蛋白水解酶，如IV型胶原酶，在肿瘤侵袭和转移中起重要作用。为检测人结肠癌中72000分子量IV型胶原酶的表达，对19例原发性结肠肿瘤的总RNA进行了印迹杂交。这些滤膜用编码72000分子量IV型胶原酶金属酶的互补DNA探针进行检测。结果以肿瘤组织中信使核糖核酸（mRNA）水平与相邻正常黏膜中mRNA水平的比值（R）表示。在18例诊断为腺癌的病例中，有13例（72%）原发性肿瘤中3.1千碱基IV型胶原酶mRNA水平高于相邻正常结肠黏膜。这些病例分为高表达（R，4.50至29.34）和中等表达（R，2.54至3.31）亚组。与5例72000分子量IV型胶原酶mRNA表达水平最低的病例（低表达亚组；R，0.96至1.48）相比，两组均显示出统计学上的显著升高（P小于0.05）。鉴于已证实在结直肠癌中72000分子量IV型胶原酶mRNA升高，我们使用免疫组织化学技术检测了其在蛋白质水平的伴随表达。使用抗72000分子量IV型胶原酶抗体对70例结肠肿瘤（包括30例良性腺瘤）进行免疫组织化学检查，结果显示与杜克分期有显著相关性（P小于0.001）。我们的结果表明，72000分子量IV型胶原酶的表达增强可能是人结肠肿瘤侵袭性的一个标志物。
