Dexamethasone modifies the susceptibility to serum cytotoxicity and increases the metastatic efficiency of a colon carcinoma cell line

Abstract

Metastatic inefficiency is a phenomenon by which a majority of tumor cells is lost in the blood stream during the metastatic process. We investigated the effects of dexamethasone (DEX), a synthesized glucocorticoid, on the serum susceptibility of a colon carcinoma cell line, HT-29, with respect to metastatic inefficiency. The susceptibility to serum cytotoxicity of these carcinoma cells is possibly an important factor in metastatic inefficiency. In this study, we used glucocorticoid because it modifies the function of the plasma membrane and has been shown to enhance the hematogenous metastasis of some tumor cells. Using HT-29 cells that had been treated with DEX in vitro, the following factors were evaluated: the metastasis of intrasplenic injected cells; in vitro and in vivo proliferation; motility; the production of matrix metalloproteinases (MMPs); and the expression of the membrane complement regulatory proteins CD46, CD55, and CD59. The number of viable cells in the liver after an intraportal injection of tumor cells was determined by the expression of human β-globin mRNA that is aberrantly expressed in HT-29 cells. In addition, we investigated 100% serum-induced proliferation, susceptibility, and apoptosis. Treatment with DEX was found to accelerate liver metastasis; here, the number of metastatic colonies and the weight of the liver were both significantly increased in DEX-treated HT-29 (HT-29DEX) cells. In contrast, there was no difference in terms of cell motility; the production of MMPs; or the expression of CD46, CD55, or CD59 between the HT-29 and HT-29DEX cells. The HT-29DEX cells exhibited enhanced proliferation in the serum, as well as resistance to cytotoxicity when exposed to 100% serum. In addition, DEX slightly inhibited serum-induced apoptosis. Finally, the expression of colon cancer-derived β-globin mRNA was detectable 24 h after intravenous injection, but only in samples obtained from the HT-29DEX-, but not in those from the HT-29-inoculated mice. These results indicate that DEX reduced the metastatic inefficiency of the HT-29 cells, resulting in a hematogenous metastasis-prone phenotype. It is thus expected that the acquisition of resistance against serum cytotoxicity is among the mechanisms that contribute to the efficiency of hematogeneous metastasis.