Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma.

The aim of this study is to investigate whether the expression of CD147 could be a prognostic factor for hepatocellular carcinoma. Tissue samples from 111 hepatocellular carcinoma patients were immunohistochemically stained with anti-CD147, anti-matrix metalloproteinases-2 and anti-vascular endothelial growth factor antibodies. Tumor microvessel density was evaluated using CD34. The survival curves were estimated by Kaplan-Meier analysis and the prognostic significance of the marker was analyzed using the log-rank test. In addition, the identification of relevant prognostic factors was performed by multivariate Cox regression analysis. CD147 was mainly expressed in cancerous lesions and its expression was positively correlated with metalloproteinases-2 (P<0.0001), vascular endothelial growth factor (P<0.0001) and microvessel density CD34 (P<0.0001). Furthermore, CD147 was significantly associated with the presence of venous invasion (P=0.0013), tumor size (P<0.0001) and pTNM tumor stages (P=0.0001), as well as serum alpha-fetoprotein level (P<0.0001). Patients with positive expression of CD147 had poorer tumor recurrence-free survival than those with negative expression of CD147 (P<0.0001). Analyzed by a proportional hazard model, strong expression of CD147 had the highest risk ratio of recurrence among these markers (P<0.0001). The findings suggest that CD147 may be a significant independent predictor of poor survival in patients with hepatocellular carcinoma, and may be involved in tumor growth, invasion and angiogenesis in hepatocellular carcinoma.

Regulation of matrix metalloproteinase production and tumor cell invasion by four monoclonal antibodies against different epitopes of HAb18G/CD147 extracellular domain.

HAb18G/CD147, a membrane spanning molecule and highly expressed in hepatocellular carcinoma (HCC) cells, was shown to stimulate the production of matrix metalloproteinases (MMPs) in the interaction of tumor cells and fibroblasts. Studies on the EMMPRIN/CD147 showed that CD147 extracellular domain is involved in the induction of MMPs. To study the biological molecular function of HAb18G/CD147 extracellular domain (HAb18G/CD147-ED) on production of MMPs following mediated tumor cell invasion, we isolated four novel monoclonal anibodies (MAbs)-1B3, 3B3, HAb18Gedomab1, and HAb18Gedomab2-against HAb18G/CD147-ED by immunization of BALB/c mice with purified HAb18G/CD147-ED fragments, which were efficiently expressed in Escherichia coli. Gelatin zymography and Boyden chamber assays were used to identify the production of MMPs in the co-cultured human fibroblast and HCC cells, and to quantify the migrated cells in the presence of the generated MAbs. The results showed that two MAbs (1B3 and 3B3) inhibited [corrected] the secretion of MMP-2 and [corrected] the HCC cell invasion, whereas the other two MAbs (HAb18Gedomab1 and HAb18Gedomab2) had reverse function [corrected] FCM additive assay showed that four MAbs recognized different epitopes of HAb18G/CD147-ED. Taken together, the results suggest that various regions of HAb18G/CD147-ED participated in the regulation of MMP secretion.