Hai-Xu Chen

Institute for Transfusion Medicine, Pittsburgh, Pennsylvania, United States

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Publications (3)15.39 Total impact

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    ABSTRACT: Recent evidence indicates that cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, for the first time, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. cDNA microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic miR-155 in HCC cells was significantly up-regulated by co-culture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the downregulation of suppressor of cytokine signaling 1 (SOCS1), leading to the subsequent activation of STAT3 signaling. This promotes the expression of MMP9, which results in increased tumor invasiveness. Conclusion: Our study reveals that S100A4 secreted from LC-MSCs, is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013.).
    Hepatology 06/2013; 57(6). DOI:10.1002/hep.26257 · 11.19 Impact Factor
  • ACTA AGRONOMICA SINICA 01/2013; 40(6):556. DOI:10.3724/SP.J.1206.2012.00576
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    ABSTRACT: Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway.
    Breast Cancer Research and Treatment 05/2011; 132(1):153-64. DOI:10.1007/s10549-011-1577-0 · 4.20 Impact Factor