NEW YORK (Reuters Health) - The number of circulating endothelial cells (CECs) or their progenitors (CEPs) may serve as a marker of the degree of angiogenesis and the effectiveness of antiangiogenic treatments, according to a report in the January issue of Cancer Cell.
“The door is now open to solving a significant problem in the development and application of antiangiogenic drugs or other types of drugs or treatments that may have an antiangiogenic effect as part of their overall mode of action,” Dr. Robert S. Kerbel from Sunnybrook and Women’s College Health Sciences Centre, Toronto, told Reuters Health. “This has been a big handicap in the field of antiangiogenic therapeutic.”
Dr. Kerbel and colleagues used a variety of approaches to determine whether circulating CECs and CEPs could be used as valid biomarkers for angiogenesis and antiangiogenic drug activity in mice.
The absolute number of CECs correlated closely with the angiogenic ability of mice, the authors report, and there was a correlation between the number of CECs and CEPs. These correlations were seen in the corneal micropocket assay, as well as a Matrigel plug perfusion assay.
Mice lacking the angiogenesis inhibitor TSP-1 showed 5-fold higher levels of CECs and CEPs, the report indicates, but treatment of these mice with the antiangiogenic drug ABT-510 markedly reduced the high levels of CEC/CEP.
Mice overexpressing the angiogenesis stimulators VEGF-A or Tie-2 receptor also showed significant increases in CEC and CEP levels, the researchers note.
In all tumor models, the investigators report, tumor-bearing mice had increased levels of both CECs and CEPs that were reduced to normal levels after treatment with the antiangiogenesis compounds DC101 or ABT-510. The tumor models included spontaneous and transplanted tumors, both solid and leukemic, in different mouse strains.
“We are planning some further studies to investigate the role of these circulating cells that we are measuring in tumor angiogenesis, and how they may be affecting not only the process of tumor angiogenesis itself, but how important they may be with respect to the mode of action of various antiangiogenic drugs or vascular targeting agents,” Dr. Kerbel said.
“In addition, we are establishing a method to help determine optimal doses of such drugs for cancer patients,” Dr. Kerbel said.
“Whether our approach will definitively solve all these problems remains to be seen, but at least it’s a promising direction,” Dr. Kerbel concluded.
Source: Cancer Cell 2005;7:101-111. [ Google search on this article ]
MeSH Headings:Biological Factors: Cell Count: Cytological Techniques: Growth Inhibitors: Health Occupations: Immunologic and Biological Factors: Investigative Techniques: Technology: Technology, Industry, and Agriculture: Technology, Medical: Tumor Markers, Biological: Biological Markers: Allied Health Occupations: Chemical Actions and Uses: Chemical Actions: Angiogenesis Inhibitors: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Biological Sciences: Chemicals and Drugs: Technology, Food and BeveragesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
