Expression of WISPs and of Their Novel Alternative Variants in Human Hepatocellular Carcinoma Cells

Abstract

WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the first time that WISP1, WISP1v, and WISP3 are expressed in HCC cell lines. Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1 delta ex3-4 and WISP3vL. Overall, our study suggests that WISP transcripts may have a role in the development of HCC, although further studies are necessary to clarify the relative importance of the expression of wild-type WISPs, as well as of their novel variants, in this tumor type.