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 α‐smooth muscle actin (α‐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 α‐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. Copyright © 1999 John Wiley & Sons, Ltd.

Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis

“…As shown using immunostaining, however, SPARC was only weakly expressed by the sinusoidal cells of non-cirrhotic livers in contrast to intense stain in the stromal cells of hepatocellular carcinoma [23]. The present immunohistochemical study was designed to reveal SPARC expression in pre-cirrhotic stages of chronic hepatitis.…”

“…SPARC expression has been reported in human livers with various fibrotic diseases such as liver cirrhosis [2,10], biliary cirrhosis of biliary atresia [22], and hepatocellular carcinoma [23]. As revealed by immunohistochemistry and in situ hybridization, SPARC was expressed by myofibroblasts in the fibrous septa of liver cirrhosis [2,22] and the capsule of hepatocellular carcinoma [23], while it was generally weak [23] or scattered in the liver parenchyma [2]. Prior to the establishment of fibrotic tissue in liver cirrhosis, fibrogenesis proceeds to various degrees with ECM deposition in the liver parenchyma during chronic hepatitis.…”

“…Prior to the establishment of fibrotic tissue in liver cirrhosis, fibrogenesis proceeds to various degrees with ECM deposition in the liver parenchyma during chronic hepatitis. There are, however, no reports on SPARC expression in the liver with chronic hepatitis except a brief description on high SPARC expression in a few patients [23]. In this study, in order to reveal SPARC expression in chronic hepatitis and its correlation with the grades of inflammatory activity and the stages of fibrosis, we immunohistochemically identified SPARC-positive cells in the liver parenchyma, and conducted quantitative analyses.…”

Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer

“…Given the varied effects of SPARC on cell adhesion and matrix integrity, it is perhaps not surprising that SPARC expression is frequently altered in a variety of tumors [13][14][15][16][17]. In addition, experimental manipulation of SPARC expression in tumor cell lines has yielded findings that suggest that SPARC promotes an invasive phenotype in prostate cancer and melanoma [16,[18][19][20][21].…”

Osteonectin Influences Growth and Invasion of Pancreatic Cancer Cells

“…19 -21 It inhibits the proliferation of a variety of cells, primarily through modulation of cell adhesion, growth factor activity, and cell cycle progression from G1 to S phase. 22 Osteonectin overexpression has been reported in a variety of human malignancies, 23 including breast, 15,24 colon, 25 esophageal, 26 prostate, 27 hepatocellular, 28 and bladder carcinomas, 29 as well as in melanomas, 30 astrocytomas, 31 and meningiomas. 32 Several in vitro and in vivo studies have linked osteonectin expression with tumor invasion; deregulated expression of osteonectin has been found to correlate with disease progression and/or poor prognosis.…”