Soluble CD44 secretion contributes to the acquisition of aggressive tumor phenotype in human colon cancer cells

Abstract

CD44, a widely distributed cell surface glycoprotein and a receptor for hyaluronan (HA), has been implicated in facilitating tumor growth and metastasis, antiapoptosis and directional motility of cancer cells. In order to investigate the role of soluble CD44 (CD44 sol) in colon cancer cell growth, SW620, a human colon cancer cell line deficient in CD44 expression was stably transfected with human CD44 cDNA containing exons 1–5, 15 and 16 of the human CD44. Western blot analyses demonstrated the presence of 78 kDa soluble CD44 protein in the culture supernatant of stably transfected cell lines (CD44 sol clones) and were not detected in the empty vector control line (clone m). The CD44 sol transfected cells showed higher cell proliferation and clonal growth in vitro, confirmed by MTT and clonogenic assays respectively, when compared to the control cells. Cell adhesion to hyaluronan was significantly lower with CD44 sol cells compared to the control cells. Western blot analyses were negative for cleaved PARP in lysates from CD44 sol cells, suggesting resistance to apoptosis. These findings indicate that the secretion of soluble CD44 contributes to colon cancer growth in vitro, possibly as a decoy receptor.