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First published online October 19, 2006
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2006-0257v1
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Submitted on April 25, 2006
Accepted on October 10, 2006

Stem Cell Genetics and Genomics

Differential Gene Expression Associated with Migration of Mesenchymal Stem Cells to Conditioned Medium From Tumor Cells or Bone Marrow Cells

Lata G. Menon 1, Sonia Picinich 2, Rajeth Koneru 3, Hui Gao 1, Siang Yo Lin 4, Mythili Koneru 5, Philipp Mayer-Kuckuk 6, John Glod 5, Debabrata Banerjee 7*

1 Department of Medicine, Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey
2 Department of Pharmacology, Graduate School of Biomedical Sciences, Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey
3 Department of Pediatric Oncology,Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey
4 Department of Pharmacology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey
5 Department of Pediatric Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey
6 Department of Pharmacology,CINJ,RWJMS,UMDNJ/Hospital for Special Surgery,NY/MSKCC,NY
7 Departments of Medicine and Pharmacology, Graduate School of Biomedical Sciences, Cancer Institute of New Jersey, Robert Wood Johnson Medical School/ University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey

* To whom correspondence should be addressed. E-mail: banerjed{at}umdnj.edu.


  Abstract

Distinct signals that guide migration of MSCs to specific in vivo targets remain unknown. We have used rat MSCs to investigate the molecular mechanisms involved in such migration. Rat MSCs were shown to migrate to tumor microenvironment in vivo and an in vitro migration assay was used under defined conditions to permit further mechanistic investigations. We hypothesized that distinct molecular signals are involved in the homing of MSCs to tumor sites and bone marrow. To test this hypothesis gene expression profiles of MSCs exposed in vitro to conditioned medium (CM) from either tumor cells or bone marrow were compared. Analysis of the microarray gene expression data revealed that 104 transcripts were upregulated in rat MSCs exposed to CM from C 85 human colorectal cancer cells for 24h versus control medium. A subset of 12 transcripts were found to be upregulated in rat MSCs that were exposed to tumor cell CM but downregulated when MSCs were exposed to bone marrow CM and included CXCL-12 (SDF-1), CXCL-2, CINC-2, Endothelial cell specific molecule-1, FGF-7, NF-{kappa}B p105 and thrombomodulin. Exposure to tumor cell CM enhanced migration of MSCs and correlated with increased SDF-1 protein production. Moreover, knockdown of SDF-1 expression in MSCs inhibited migration of these cells to CM from tumor cells, but not bone marrow cells, confirming the importance of SDF-1 expression by MSCs in this differential migration. These results suggested that increased SDF-1 production by MSCs acts in an autocrine manner and is required for migratory responses to tumor cells.

Key Words. in vivo migration, gene expression, SDF-1, microenvironment, chemotaxis, SDF-1, 0




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