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 wei ght isoforms (especially CD44v6), as well as down-regulation of standard CD 44 (CD44s), are postulated to result in increased tumourigenicity. We studi ed the metastatic phenotype produced by the expression of CD44s by stable t ransfection 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 ani mals were sacrificed at 6 weeks after injection and morphological end-point s relating to macrometastases and micrometastases were studied. CD44s expre ssion was associated with decreased development of macroscopic tumours (0.9 vs 3.0 tumours! mouse liver, p=0.004), less extensive tumour replacement o f the liver (2.6% vs 12.8%, p=0.04) and decreased numbers of micrometastase s (3.8 x 10(-8) vs 7.9 x 10-8 micrometastases/mum(2) p=0.2). This study is the first to demonstrate the mitigating effect of CD44s expression on the h epatic metastatic phenotype in a colorectal carcinoma cell line that does n ot ordinarily express CD44.