No abstract

RhoA, a member of the Rho

BackgroundHuman umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC).MethodshUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mice to observe the effects of hUCMSCs on tumor establishment. hUCMSCs injected through the caudal vein to the mice with pre-established EC to observe the effects of hUCMSCs on tumor outgrowth. In order to elucidate the underlying mechanisms, we also performed in vitro experiments including directly co-culture, transwell assay, proliferation assay and western blotting analysis.ResultshUCMSCs promoted EC formation in nude mice. In the in vivo model of pre-established EC, intravenously injected hUCMSCs potently promoted tumor growth. When in vitro co-cultured with hUCMSCs, EC cells proliferation increased. After co-cultured with hUCMSCs through transwell system, EC cells showed increased proliferation. Through transwell assay, we also observed that EC cells recruited MSCs, and MSCs promoted EC cells migration and invasion. Western blotting data showed that the expressions of proliferation related proteins Bcl-2, survivin and metastasis related proteins MMP-2 and MMP-9 were up-regulated in the EC cells transwell co-cultured with hUCMSCs.ConclusionsOur results indicated that hUCMSCs could favor tumor growth in vivo and in vitro. Thus, the exploitation of hUCMSCs in new therapeutic strategies should be cautious under the malignant conditions.

Previous studies have shown that RhoE, an atypical member of the Rho GTPase family, may play an opposite role to RhoA in regulating cell proliferation and invasion. To explore the relationship between RhoE and the malignant phenotypes of human cancer, we have determined the expression patterns of RhoE in varying grade of human cancer tissues and tested the effects of RhoE expression in several RhoE underexpressing cancer cell lines. Systemic immunocytochemistry analyses of gastric, colorectal, lung and breast carcinomas, respectively, showed that RhoE protein expression was significantly decreased in most cancer cases compared with that of adjacent normal tissues. Enhanced RhoE expression could markedly inhibit proliferation, migration and invasion and induce apoptosis of the cancer cells which have relatively low levels of endogenous RhoE expression. Wild-type p53 (wt-p53) could strongly increase RhoE expression in p53-transfected cells. Furthermore, the luciferase assays indicated that wt-p53 significantly enhanced the activities of RhoE promoter compared with mutant p53 (mt-p53) in PC3 cells (p53 null). Collectively, data are presented showing that RhoE may participate in human cancer progression and act as a candidate target of p53, and these findings also strongly suggest that RhoE may be a new candidate tumor suppressor and could serve as a potential target in the gene therapy of cancer.