Association of tumor-associated fibroblasts with progression of hepatocellular carcinoma

Interaction between tumor and stromal cells plays an important role in cancer progression. The aim of this study was to explore the effects of tumor-associated fibroblasts on regulation of hepatocellular carcinoma (HCC) progression. Sixty-five cases of HCC and the corresponding normal liver tissues were recruited for immunohistochemical assessment of α-smooth muscle actin (α-SMA) expression, a biomarker for activated fibroblasts. Clinicopathological data were also collected from HCC patients for association with α-SMA expression. Primary cell culture of fibroblasts from HCC tissues was used to generate conditioned medium for testing the effect on regulation of HCC cell migration capacity in the transwell cell migration assay. α-SMA protein was expressed in 84.0 % (21 out 25 cases) of the fibroblasts from the metastatic HCCs, 45 % (18/40) from HCCs without metastasis, and 19.2 % (5/26) from normal liver tissues, difference of which was statistically significant (P < 0.01). The expression of α-SMA protein in HCC tissues was associated with tumor thrombosis, poor pathology grade, advanced clinical stages, and lymph node metastasis. The conditioned medium from the primary cultured fibroblasts with α-SMA expression significantly promoted the migration capacity of HCC Hep3B cells compared to the heat-inactivated conditioned medium. The data from the current study demonstrated that expression of α-SMA protein in HCC fibroblasts associated with tumor metastasis and advanced clinical stages and that the conditioned medium from α-SMA-positive fibroblasts enhanced HCC cell migration. This study indicates that α-SMA protein might serve as a biomarker to predict HCC progression.