title: Increased migration of human mesenchymal stromal cells by autocrine motility factor (AMF) resulted in enhanced recruitment towards hepatocellular carcinoma.
abstract: OBJECTIVE
  Several reports described the migration of human mesenchymal stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The aim of this study was to analyze AMF involvement on MSC migration towards human HCC.
  
  
  METHODS
  Production of AMF by HCC tumors was evaluated by western analysis. The effects of AMF on MSCs from different sources (bone marrow, adipose tissue and perivascular cells from umbilical cord) were analyzed using in vitro migration assay; metalloproteinase 2 (MMP2) activity and expression of critical genes were studied by zymography and qRT-PCR, respectively. To assess AMF involvement on the in vivo MSC migration, noninvasive fluorescence imaging was performed. To test the effect of AMF-primed MSCs on tumor development, in vitro proliferation and spheroids growth and in vivo tumor volume were evaluated.
  
  
  RESULTS
  AMF produced by HCC was found to induce migration of different MSCs in vitro and to enhance their MMP2 activity. Stimulation of MSCs with recombinant AMF (rAMF) also induced the in vitro adhesion to endothelial cells in coincidence with changes in the expression levels of MMP3, AMF receptor, caveolin-1, and -2 and GDI-2. Importantly, stimulation of MSCs with rAMF increased the in vivo migration of MSCs towards experimental HCC tumors. AMF-priming of MSCs did not induce a pro-tumorigenic effect on HCC cells neither in vivo nor in vitro.
  
  
  CONCLUSIONS
  AMF plays a role in MSC recruitment towards HCC. However, its ability to increase MSC migration to HCC for therapeutic purposes merits further evaluation.
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Bayo
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Esteban
authors.initials: E
authors.lastname: Fiore
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina.
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Aquino
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Malvicini
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Manglio
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Estanislao
authors.initials: E
authors.lastname: Peixoto
authors.affiliation: Liver Unit, Hospital Universitario Austral, Universidad Austral, Derqui-Pilar, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Andriani
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Alaniz
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Flavia
authors.initials: F
authors.lastname: Piccioni
authors.affiliation: CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir, Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Bolontrade
authors.affiliation: CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir, Buenos Aires, Argentina.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Podhajcer
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Garcia
authors.affiliation: Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Pilar, Buenos Aires, Argentina; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina; Liver Unit, Hospital Universitario Austral, Universidad Austral, Derqui-Pilar, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism* / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D047368:Tumor Burden
chemical_list: D008666:Metalloendopeptidases; D005956:Glucose-6-Phosphate Isomerase
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