Osteonectin/SPARC is overexpressed in human hepatocellular carcinoma

Abstract

Osteonectin (ON)/SPARC is a glycoprotein involved in extracellular matrix remodelling. ON expression by myofibroblasts has been reported in fibrotic human liver. As ON also plays a role in cell adhesion, differentiation, and proliferation, this study was designed to document its expression in human hepatocellular carcinoma (HCC). Tissues from 26 HCCs of various histological grades and architecture and from surrounding non-tumour liver (23 cirrhotic or fibrotic, three non-fibrotic) were tested by in situ hybridization and immunohistochemistry. Immunohistochemical detection of alpha-smooth muscle actin (alpha-SMA) was performed on serial sections or in combination with hybridization. Large amounts of ON mRNA and protein were detected in the tumour capsule, in the fibrous bands, and along capillaries within HCCs. The signal was located in cells suggestive of myofibroblasts, as confirmed by positive staining for alpha-SMA. In HCC, ON protein was always detectable, with strong staining in high-grade tumours, whereas it was mostly undetectable in non-tumour tissues. A clear difference was also shown for ON transcripts, except in a few cases with chronic active hepatitis, where ON transcripts were also expressed at a high level. Overexpression of ON transcripts in HCC vs. non-tumour liver was confirmed by RNA blot in 20/22 patients tested. In conclusion, ON is strongly expressed by the stromal myofibroblasts of human HCC, especially of high grade. This expression could play a role in tumour progression.