Increased Migration of Human Mesenchymal Stromal Cells by Autocrine Motility Factor (AMF) Resulted in Enhanced Recruitment towards Hepatocellular Carcinoma

被引：42

作者：

Bayo, Juan ^{[1
]}

Fiore, Esteban ^{[1
]}

Aquino, Jorge B. ^{[1
,2
]}

Malvicini, Mariana ^{[1
]}

Rizzo, Manglio ^{[1
]}

Peixoto, Estanislao ^{[1
]}

Andriani, Oscar ^{[3
]}

Alaniz, Laura ^{[1
,2
]}

Piccioni, Flavia ^{[1
]}

Bolontrade, Marcela ^{[2
,4
]}

Podhajcer, Osvaldo ^{[2
,4
]}

Garcia, Mariana G. ^{[1
,2
]}

Mazzolini, Guillermo ^{[1
,2
,3
]}

机构：

[1] Univ Austral, Fac Ciencias Biomed, Gene Therapy Lab, Buenos Aires, DF, Argentina

[2] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina

[3] Univ Austral, Hosp Univ Austral, Liver Unit, Derqui Pilar, Argentina

[4] Fdn Inst Leloir, Mol & Cellular Therapy Lab, Buenos Aires, DF, Argentina

来源：

PLOS ONE | 2014年 / 9卷 / 04期

关键词：

STEM-CELLS; GENE-EXPRESSION; IN-VITRO; MATRIX METALLOPROTEINASE-3; INFLAMMATORY CYTOKINES; UP-REGULATION; TISSUE; ACTIVATION; RECEPTOR; GROWTH;

D O I：

10.1371/journal.pone.0095171

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background and Aims: 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. Conclusion: AMF plays a role in MSC recruitment towards HCC. However, its ability to increase MSC migration to HCC for therapeutic purposes merits further evaluation.

引用

页数：10

共 37 条

[1]

THE DIAGNOSTIC VALIDITY OF THE SERUM TUMOR-MARKER PHOSPHOHEXOSE ISOMERASE (PHI) IN PATIENTS WITH GASTROINTESTINAL, KIDNEY, AND BREAST-CANCER [J].

BAUMANN, M ;

KAPPL, A ;

LANG, T ;

BRAND, K ;

SIEGFRIED, W ;

PATEROK, E .

CANCER INVESTIGATION, 1990, 8 (3-4) :351-356

[2]

Bayo J, 2013, LIVER INT

[3]

Mesenchymal Stromal Cells A Novel Treatment Modality for Tissue Repair [J].

Bernardo, Maria Ester ;

Locatelli, Franco ;

Fibbe, Willem E. .

HEMATOPOIETIC STEM CELLS VII, 2009, 1176 :101-117

[4]

Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3 [J].

De Becker, Ann ;

Van Hummelen, Paul ;

Bakkus, Marleen ;

Vande Broek, Isabelle ;

De Wever, Joke ;

De Waele, Marc ;

Van Riet, Ivan .

HAEMATOLOGICA, 2007, 92 (04) :440-449

[5]

Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas [J].

Dobashi, Y. ;

Watanabe, H. ;

Sato, Y. ;

Hirashima, S. ;

Yanagawa, T. ;

Matsubara, H. ;

Ooi, A. .

JOURNAL OF PATHOLOGY, 2006, 210 (04) :431-440

[6]

Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].

Dominici, M. ;

Le Blanc, K. ;

Mueller, I. ;

Slaper-Cortenbach, I. ;

Marini, F. C. ;

Krause, D. S. ;

Deans, R. J. ;

Keating, A. ;

Prockop, D. J. ;

Horwitz, E. M. .

CYTOTHERAPY, 2006, 8 (04) :315-317

[7]

Ferenci P, 2010, J GASTROINTEST LIVER, V19, P311

[8]

Activation of Signal Transducers and Activators of Transcription 3 and Focal Adhesion Kinase by Stromal Cell-Derived Factor 1 Is Required for Migration of Human Mesenchymal Stem Cells in Response to Tumor Cell-Conditioned Medium [J].

Gao, Hui ;

Priebe, Waldemar ;

Glod, John ;

Banerjee, Debabrata .

STEM CELLS, 2009, 27 (04) :857-865

[9]

Human mesenchymal stem cells overexpressing pigment epithelium-derived factor inhibit hepatocellular carcinoma in nude mice [J].

Gao, Y. ;

Yao, A. ;

Zhang, W. ;

Lu, S. ;

Yu, Y. ;

Deng, L. ;

Yin, A. ;

Xia, Y. ;

Sun, B. ;

Wang, X. .

ONCOGENE, 2010, 29 (19) :2784-2794

[10]

Hepatocellular Carcinoma Cells and Their Fibrotic Microenvironment Modulate Bone Marrow-Derived Mesenchymal Stromal Cell Migration in Vitro and in Vivo [J].

Garcia, Mariana G. ;

Bayo, Juan ;

Bolontrade, Marcela F. ;

Sganga, Leonardo ;

Malvicini, Mariana ;

Alaniz, Laura ;

Aquino, Jorge B. ;

Fiore, Esteban ;

Rizzo, Manglio M. ;

Rodriguez, Andres ;

Lorenti, Alicia ;

Andriani, Oscar ;

Podhajcer, Osvaldo ;

Mazzolini, Guillermo .

MOLECULAR PHARMACEUTICS, 2011, 8 (05) :1538-1548

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