Endothelial Progenitor Cells May Spur Tumor Regrowth
Primary therapy may cause progenitor-cell spike that could be inhibited by anti-angiogenic drugs
WEDNESDAY, Sept. 27 (HealthDay News) -- Use of vascular disrupting agents for tumor treatment leads to a spike in circulating endothelial progenitor cells that home to the tumor rim and allow tumor regrowth, according to a report in the Sept. 22 issue of Science. Targeting these progenitor cells with anti-angiogenic drugs may help enhance therapy, the authors suggest.
Robert Kerbel, Ph.D., of Sunnybrook Health Sciences Centre in Toronto, Canada, and colleagues studied mice with experimental tumors that were treated with a vascular disrupting agent called OXi-4503. They found that shortly after treatment, circulating endothelial progenitor cell levels increased and were eventually found at the tumor rim.
Treating the mice with an anti-angiogenic monoclonal antibody called DC101 shortly after OXi-4503, reduced the accumulation of circulating endothelial progenitor cell at the tumor rim and cut tumor size by over half. The tumors that did develop showed reduced blood flow and increased necrosis and hypoxia compared with controls. Mice unable to mobilize circulating endothelial progenitor cells showed hypoxic tumors even without anti-angiogenic therapy, confirming the major role of circulating endothelial progenitor cells in tumor regrowth.
Although circulating endothelial progenitor cell levels are low in untreated tumors, the levels can rise rapidly in response to stresses like drug treatment. "Consideration should be given to the counterintuitive idea of administering chemotherapy shortly after vascular disrupting agent treatment, rather than the opposite sequence, because of the ability of chemotherapy to target circulating endothelial progenitor cells," they write.
The study was partly supported by grants from ImClone Systems, Inc., and VisualSonic.