Tumor Microenvironment Effectively Targeted to Block Cancer Growth

Using advanced high-resolution microscopy and flow cytometry, the researchers narrowed in on the earliest stages of cancer progression and identified the role of EPCs in generating blood vessels that allow cancers to grow.

"If we selectively blocked the EPCs, tumors were unable to make blood vessels and could not sustain their own growth,” said Dr. Vivek Mittal, assistant professor at Cold Spring Harbor Laboratory (CSHL; Cold Spring Harbor, NY, USA).

The results open an entirely new field of research on how vascular progenitor cells control tumor growth and highlight their potential for cancer therapeutics. Published in the June 15, 2007, issue of the journal Genes & Development by CSHL researchers led by Dr. Daniel Nolan and assistant professor Dr. Mittal, the study resolves a debate in the field of angiogenesis that has resulted from years of conflicting findings about the existence of EPCs in cancerous tumors. Until now, this field of research that focuses on new blood vessel development has been divided between researchers who have suggested the existence of EPCs and those who have strongly disputed their presence.

The CSHL study theorizes that those who did not find evidence of EPCs in tumors were in all probability looking for them in later stages of tumor progression when EPCs are diluted by host endothelial cells. The new findings show that EPCs are only present in the earliest stages of tumor progression, before the formation of blood vessels. "We found that the role of EPCs is to direct the formation and organization of the vascular structure that ultimately feeds the tumor as it grows,” said Dr. Nolan.

Using antibodies developed for angiogenic cancer treatment, CSHL researchers collaborated with Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) and were able to remove EPCs without harming normal blood vessels. This has considerable clinical potential, especially in combating cancer re-growth after incomplete surgical resection or chemotherapy.

"The exciting news is that targeting such a minor population of the BM-derived tumor microenvironment has such a dramatic impact on tumor progression,” said Dr. Mittal. The study shows that in addition to developing therapies that directly target cancer cells, it is also as important to develop therapies that target critical non-cancerous cells such as EPCs.


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Cold Spring Harbor Laboratory