Stromal cells expressing elevated VCAM-1 enhance survival of B lineage tumor cells.
In the current study we generated murine bone marrow stromal cells that constitutively express human VCAM-1. These stromal cell lines allow investigation of the contribution of VCAM-1 initiated signaling to tumor cell survival. Co-culture of ALL cell lines with stromal cells engineered to over express VCAM-1 enhanced survival of leukemic cells in a PI-3 kinase-dependent manner, compared to co-culture with parental stromal cells expressing only endogenous VCAM-1. These observations suggest that modulation of stromal cell VCAM-1 by specific chemotherapeutic drugs may have utility in decreasing residual disease. In addition, these novel lines provide an in vitro model in which other tumor types that interact with stromal cells in the bone marrow microenvironment may be evaluated to determine the contribution of VCAM-1 initiated signaling to modulation of treatment response.
Hall
Brett M
BM
Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA.
Fortney
James E
JE
Taylor
Lela
L
Wood
Hillary
H
Wang
Lin
L
Adams
Scott
S
Davis
Suzanne
S
Gibson
Laura F
LF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D018920:Coculture Techniques; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D019010:Vascular Cell Adhesion Molecule-1; D005047:Etoposide; D019869:Phosphatidylinositol 3-Kinases