The role of stem cells in malignant disease is a rapidly emerging topic. The current study characterized bone marrow-derived mesenchymal stem cells (MSC) for properties that might contribute to malignancy. Using fluorescence-activated flow cytometry and immuno-staining MSC express several cell surface markers including ICAM-1, VCAM and CD44. MSC and endothelial precursor cells also share several cell surface markers including P1H12, CD105 and PDGFR. RT-PCR for a series angiogenesis and invasion markers detected expression of VEGF and MMP-2 by MSC but no expression of ANG-2, MMP-1, MMP-9, bFGF, IGF, HGF and TGF-β. The secretion of cytokines and growth factors by MSC into culture media was characterized using multiplex Bioplex technology. In a 22-plex assay, IL-6, IL-8, IL-12(p40), MCP-1, SDF-1 and VEGF were readily detected. Like endothelial cells and pericytes, MSC form tubes/networks on Matrigel, although this property is lost after 5-6 passages in culture. bFGF and PDGF (30-125 ng/ml, 72 hrs) promoted MSC proliferation. The kinase inhibitors, SU6668 and SU11248, decreased MSC proliferation in a concentration dependent fashion. However, Avastin did not alter MSC proliferation. The influence of MSC in a co-culture assay with colon cancer cells (HT29, DLD-1 and SW480) in a collagen plug was assessed. While HT29 cultures were not altered by MSC, DLD-1 clusters were invaded by MSC and SW480 were surrounded by MSC colonies. Serial analysis of gene expression (SAGE) of the colon cancer cell lines will be used to identify potential factors that may account for these differences. Co-implantation of MSC with colon cancer cells in vivo will be carried out to examine the effects of MSC on tumor growth. These results support the notion that MSC may have a role in malignant tumor growth and progression.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]