Do mesenchymal stem cells (MSC) help to slow solid-tumor growth, or accelerate it? A new study of MSCs in human solid-tumor samples sheds light on the controversy by pinpointing carcinoma-associated MSCs (CA-MSC) that assist in expanding ovarian tumors.
University of Michigan scientists found CA-MSCs in 14 of 15 primary human ovarian cancer tumor samples (J Clin Invest 2011;121:3206–19). These cells were nontumorigenic and, like MSCs from normal cells, could differentiate into adipose tissue, bone, or cartilage. Their gene expression patterns, however, differed from those of MSCs from normal cells, with significantly greater expression of bone marrow protein (BMP) growth factor proteins.
When injected into immunocompromised mice, the CA-MSCs promoted tumor growth more than did control MSCs. Further, both in vitro and in vivo tests suggested that CA-MSCs boost production of cancer stem cells. Production of cancer stem cells also climbed in separate tests when tumor cells were treated with BMP family member BMP2. Conversely, treating tumor cells with the BMP inhibitor Noggin partially cut the CA-MSC effect on cancer stem cell production, suggesting BMP signaling may be a therapeutic target.
Given the important role of the BMP family in maintaining healthy bones, treating ovarian cancer by systematically delivering BMP inhibitors may not be workable. “But you might be able to target therapy to the tumor vascular niche, where the mesenchymal stem cells and cancer stem cells live, with signaling peptides or nanoparticles or another mechanism,” says senior author Ronald Buckanovich, MD, PhD.
