Effects of down-regulation of integrin-β₁ expression on migration and hepatic metastasis of human colon carcinoma

Abstract

Organ-specific tumor cell adhesion to extracellular matrix (ECM) components and cell migration into host organs often involve integrin-mediated cellular processes. Direct integrin-mediated cell adhesion to ECM components in the space of Disse appears to be required for the successful liver metastatic formation of colon cancer. In the present study, human colon cancer HT-29 cells were transfected by liposome with integrin-β₁ antisense oligodeoxynucleotide (ASODN). The integrin-β₁ gene expression in HT-29 cells was significantly down-regulated. The migration of HT-29 cells was assayed using transwell cell culture chambers in vitro. The number of migrating HT-29 cells in experimental group was far less than that in control group (P<0.05). The models of hepatic metastasis in nude mice were established by the intrasplenic injection of transfected HT-29 cells. Thirty days later, the nude mice were killed and the average number of hepatic metastases (4.00±0.93 per mouse), average volume (10.10±6.50 mm³ per mouse), average weight (0.0440±0.0008 g per mouse) in experimental group were remarkably reduced as compared with those in control group (P<0.05). Integrin-β₁ expression in the hepatic metastasis was studied by immunohistochemistry (SP). Positive cell percentage of hepatic metastases in experimental group was markedly decreased as compared with that in control group (P<0.05). It was concluded that integrin-β₁ may take part in hepatic metastasis, and down-regulation of integrin-β₁ expression may play a key role in decreasing migration and hepatic metastasis of human colon carcinoma cells (HT-29).

Keywords

hepatic metastasis / colon carcinoma / integrin-β₁

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