Chemokine CCL15 Mediates Migration of Human Bone Marrow-Derived Mesenchymal Stem Cells Toward Hepatocellular Carcinoma

Stem Cells
Y GaoXuehao Wang

Abstract

Mesenchymal stem cells (MSCs) possess the ability to migrate toward tumor sites and are regarded as promising gene delivery vehicles for cancer therapeutics. However, the factors that mediate this tropism have yet to be completely elucidated. In this study, through cytokine array analysis, chemokine CCL15 was found to be the most abundant protein differentially expressed in hepatocellular carcinoma (HCC) cell lines compared with a normal liver cell line. Serum CCL15 levels in HCC patients determined by enzyme linked immunosorbent assay were shown to be profoundly elevated compared with healthy controls. Immunohistochemical analysis indicated that CCL15 expression was much stronger in HCC tumor tissues than in adjacent nontumor tissues. Transwell migration assay suggested that CCL15 may be involved in chemotaxis of human MSCs (hMSCs) toward HCC in vitro and that this chemotactic effect of CCL15 is mediated via CCR1 receptors on hMSCs. Orthotopic animal models of HCC were established to investigate the role of CCL15 in hMSCs migration toward HCC in vivo. Both histological and flow cytometric analysis showed that significantly fewer hMSCs localized within 97H-CCL15-shRNA xenografts compared with 97H-green fluorescent protein xenog...Continue Reading

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Citations

Aug 3, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Long-Zi LiuQiang Gao
Jun 9, 2017·Molecular and Cellular Biochemistry·Vikrant RaiDevendra K Agrawal
Dec 11, 2020·Carcinogenesis·Xiongfeng PanAizhong Liu
Nov 14, 2020·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Jun 18, 2021·Stem Cell Reviews and Reports·Alison R Mercer-SmithShawn D Hingtgen
Aug 16, 2019·Respiration; International Review of Thoracic Diseases·Masako WatanabeNoboru Hattori

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