Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.
Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.
复制标题
通过反义抑制 MUC2 粘蛋白合成，可以减少人结肠癌细胞在肝脏中的定植。
DOI：
10.1016/s0016-5085(99)70133-2
复制
发表时间：
1999
期刊：
影响因子：
29.4
通讯作者：
Bresalier,RS
中科院分区：
文献类型：
--
作者：
Sternberg,LR;Byrd,JC;Yunker,CK;Dudas,S;Hoon,VK;Bresalier,RS
Background & AimsAlterations in the production of epithelial mucins have been correlated with advanced tumor stage in the colon, but direct evidence for a role of specific mucin genes in liver metastasis is lacking. The current study was designed to establish more directly the role of MUC2 in colon cancer metastasis.MethodsMUC2 levels were manipulated in highly metastatic human colon cancer cells using eukaryotic expression constructs designed to express a portion of MUC2 complementary DNA in antisense orientation. To assess the effect of MUC2 levels on metastatic potential, liver colonization was assessed in athymic mice after splenic-portal inoculation.ResultsStable integration of the MUC2 antisense construct into metastatic colon cancer cells (LS LiM6) resulted in an 80% reduction in MUC2-specific messenger RNA and a concomitant decrease in MUC2 apomucin protein. This reduction was associated with a 50% reduction in synthesis of mature glucosamine-labeled mucin, almost complete inhibition of secretion of sialyl-LeXand sialyl-Tn antigens, and a 40% decrease in binding of colon cancer cells to E-selectin. Reduction in MUC2 levels was associated with a marked decrease in liver colonization.ConclusionsThis study provides direct evidence that MUC2 plays an important role in colon cancer metastasis. GASTROENTEROLOGY 1999;116:363-371
