Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues
Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues
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DOI：
10.1073/pnas.93.25.14827
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发表时间：
1996-12-10
影响因子：
11.1
通讯作者：
Waldman, SA
中科院分区：
文献类型：
--
作者：
Carrithers, SL;Barber, MT;Waldman, SA
鸟苷酸环化酶C（GCC）仅在胎盘哺乳动物的肠黏膜和结肠癌细胞中被检测到。然而，在有袋类动物的一些组织中也发现了这种受体，并且有研究表明在胎盘哺乳动物的肠道以外的组织中也有其表达。肠道外组织中的结直肠肿瘤细胞选择性表达GCC，这将使该受体能够用作转移性疾病的选择性标志物。因此，对人体组织和肿瘤中的GCC表达进行了检测，并将受体功能与通过聚合酶链反应（PCR）的检测结果相关联。通过配体结合和催化激活，在正常肠道以及原发性和转移性结直肠肿瘤中检测到了GCC，但在肠道外组织或肿瘤中未检测到。同样，对来自正常肠道以及原发性和转移性结直肠肿瘤的样本进行PCR，得到了GCC特异性扩增产物，但肠道外组织或肿瘤的样本则没有。使用GCC特异性探针进行的Northern杂交分析显示，在正常肠道以及原发性和转移性结直肠肿瘤中有一个约4kb的转录本，与重组GCC相对应，但在肠道外组织中没有。因此，GCC在人类的肠道和结直肠肿瘤中选择性表达，并且似乎是正常组织中转移性癌细胞的一个相对特异性的标志物。实际上，对GCC进行PCR检测发现，一些Dukes B期结直肠癌患者以及所有接受检测的Dukes C期和Dukes D期结直肠癌患者的血液中存在肿瘤细胞，但在正常受试者或Dukes A期结肠癌患者或其他非恶性肠道疾病患者的血液中未检测到。
Guanylyl cyclase C (GCC) has been detected only in intestinal mucosa and colon carcinoma cells of placental mammals. However, this receptor has been identified in several tissues in marsupials, and its expression has been suggested in tissues other than intestine in placental mammals, Selective expression of GCC by colorectal tumor cells in extraintestinal tissues would permit this receptor to be employed as a selective marker for metastatic disease. Thus, expression of GCC was examined in human tissues and tumors, correlating receptor function with detection by PCR. GCC was detected by ligand binding and catalytic activation in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues or tumors. Similarly, PCR yielded GCC-specific amplification products with specimens from normal intestine and primary and metastatic colorectal tumors, but not from extraintestinal tissues or tumors. Northern blot analysis employing GCC-specific probes revealed an approximate to 4-kb transcript, corresponding to recombinant GCC, in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues. Thus, GCC is selectively expressed in intestine and colorectal tumors in humans and appears to be a relatively specific marker for metastatic cancer cells in normal tissues. Indeed, PCR of GCC detected tumor cells in blood from some patients with Dukes B colorectal cancer and all patients examined with Dukes C and D colorectal cancer, but not in that from normal subjects or patients with Dukes A colon carcinoma or other nonmalignant intestinal pathologies.