Abstract
<div>Abstract<p>Colon cancer cells express the carbohydrate determinant sialyl Lewis<sup>x</sup>, while they exhibit markedly decreased the expression of its sulfated derivative, sialyl 6-sulfo Lewis<sup>x</sup>. In contrast, normal colonic epithelial cells strongly express sialyl 6-sulfo Lewis<sup>x</sup>, but they virtually do not express sialyl Lewis<sup>x</sup>. Impaired sulfation was therefore suggested to occur during the course of malignant transformation of colonic epithelial cells and was assumed to be responsible for the increased sialyl Lewis<sup>x</sup> expression in cancers. To elucidate the molecular biological background of the impaired sulfation in cancers, we studied the expression levels of mRNA for 6-<i>O</i>-sulfotransferase isoenzymes, PAPS synthases and transporters, and a cell membrane sulfate transporter, DTDST, in cancer tissues. The most striking decrease in cancer cells compared with nonmalignant epithelial cells was noted in the transcription of the <i>DTDST</i> gene (<i>P</i> = 0.0000014; <i>n</i> = 20). Most cultured colon cancer cells had a diminished <i>DTDST</i> transcription, which was restored when cultured with histone deacetylase inhibitors. Suppression of <i>DTDST</i> transcription under the control of a tet-off inducible promoter resulted in increased sialyl Lewis<sup>x</sup> expression and reduced sialyl 6-sulfo Lewis<sup>x</sup> expression. Unexpectedly, the growth rate of the cancer cells was markedly enhanced when transcription of <i>DTDST</i> was suppressed. These results show that the decrease in the transcription of the sulfate transporter gene is the major cause of decreased expression of sialyl 6-sulfo Lewis<sup>x</sup> and increased expression of sialyl Lewis<sup>x</sup> in colon cancers. The results also suggest that the diminished <i>DTDST</i> expression is closely related to enhanced proliferation of cancer cells. Cancer Res; 70(10); 4064–73. ©2010 AACR.</p></div>
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