CD44s expression mitigates the phenotype of human colorectal cancer hepatic metastases

Alterations in expression of the CD44 adhesion protein have been implicated in colorectal tumourigenesis. Overexpression of variant high molecular weight isoforms (especially CD44v6), as well as down-regulation of standard CD44 (CD44s), are postulated to result in increased tumourigenicity. We studied the metastatic phenotype produced by the expression of CD44s by stable transfection into a human colorectal carcinoma cell line, SW620, that shows absence of any CD44 expression. Splenic injection of 2 x 10(6) SW620 colon cancer cells into SCID mice was used to produce hepatic metastases. The animals were sacrificed at 6 weeks after injection and morphological end-points relating to macrometastases and micrometastases were studied CD44s expression was associated with decreased development of macroscopic tumours (0.9 vs 3.0 tumours/ mouse liver, p = 0.004), less extensive tumour replacement of the liver (2.6% vs 12.8%, p = 0. 04) and decreased numbers of micrometastases (3.8 x 10(-8) vs 7.9 x 10(-8) micrometastases/ microm2, p = 0.2). This study is the first to demonstrate the mitigating effect of CD44s expression on the hepatic metastatic phenotype in a colorectal carcinoma cell line that does not ordinarily express CD44.