title: Trafficking mechanism of bone marrow-derived mesenchymal stem cells toward hepatocellular carcinoma HepG2 cells by modulating Endoglin, CXCR4 and TGF-β.
abstract: Mesenchymal stem cells (MSCs) display differential migration ability toward different tumor-released factors. Migration of MSCs is highly important in induction of proliferation and invasiveness of hepatocellular carcinoma (HepG2) cells. In this study, the role of CXCR4/CXCL12 axis and TGF-βR signaling were evaluated in the migration of MSCs toward HepG2 cells. The MSCs were incubated with SDF-1α (CXCL12), antagonists of CXCR4, TGF-βR, and co-receptor of TGF-β, (endoglin) for 48h. Then, the migration of these cells toward HepG2 cells was analyzed using in vitro migration assay. SDF-1α at a concentration of 100nM MSCs revealed the highest migration rate toward the conditioned medium (1.62 fold compared to the migration of un-treated MSCs; p<0.05). Applying combination of the antagonists against CXCR4, TGF- βR, and co-receptor of TGF-β decreased the migration rate significantly (4.51 fold; p<001). Western blot analysis confirmed that RhoA activity is a core modulator in migration pathway. This study demonstrated that CXCR4 and TGF-βR signaling are important for migration of MSCs toward HepG2 cells. Identifying the key mediators in the migration of MSCs toward hepatocellular carcinoma cells and then development of the therapeutic inhibitors against these factors can be considered as an essential strategy in suppression of tumor progression and metastasis.
authors.affiliation: Tabriz University of Medical Sciences Liver and Gastrointestinal Diseases Research Center Tabriz Iran.
authors.forename: A
authors.initials: A
authors.lastname: Mardomi
authors.affiliation: Tabriz University of Medical Sciences Students' Research Committee Tabriz Iran.
authors.forename: M
authors.initials: M
authors.lastname: Sabzichi
authors.affiliation: Tabriz University of Medical Sciences Liver and Gastrointestinal Diseases Research Center Tabriz Iran.
authors.forename: M
authors.initials: M
authors.lastname: Hussein Somi
authors.affiliation: Tabriz University of Medical Sciences Immunology Research Center Tabriz Iran.
authors.forename: D
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: Tabriz University of Medical Sciences Umbilical Cord Stem Cell Research Center Tabriz Iran.
authors.forename: R
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Tabriz University of Medical Sciences Liver and Gastrointestinal Diseases Research Center Tabriz Iran.
authors.forename: O
authors.initials: O
authors.lastname: Taj Sanjarani
authors.affiliation: Tabriz University of Medical Sciences Liver and Gastrointestinal Diseases Research Center Tabriz Iran drnsamadi@yahoo.com.
authors.forename: N
authors.initials: N
authors.lastname: Samadi
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D001596:Benzylamines; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D000080027:Cyclams; D000071063:Endoglin / Q000378:metabolism*; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C509927:4-(4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide; D001549:Benzamides; D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D000080027:Cyclams; D000071063:Endoglin; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta; D020742:rhoA GTP-Binding Protein; C088327:plerixafor