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Mosaic blood vessels
Implications for drug delivery, metastasis and cancer therapy
By Bijal P. Trivedi

In a recent study, Harvard scientists found that many blood vessels in tumors are a mosaic of normal endothelial cells and tumor cells. This incorporation of tumor cells into the vessel architecture has significant implications for the design and delivery of anti-cancer drugs, and possibly diagnostics.

Left: A red fluorescent tag binds to endothelial cells lining the inside of the blood vessel. The tumor is shown in green. The arrow indicates where tumor now makes up part of the vessel.

The study revealed that 15 percent of blood vessels in human colon cancers contain tumor cells. In fact, tumor cells cover about four percent of the inner surface area of these mosaic vessels. Whether this is the case for other types of tumors has not yet been explored.

Lance Munn, of Harvard Medical School and one of the authors of the paper, calculates that the tumor cells are shed into the blood stream within two days. This is consistent with previous research suggesting that every day one million tumor cells per gram of tumor are shed into the circulation.

The "most provocative implication" of Munn's research, according to Judah Folkman of Harvard Medical School, is the opportunity to analyze circulating tumor cells that have been shed from mosaic vessels. "In the foreseeable future, such molecular methods could possibly diagnose cancer before it can be located by conventional imaging techniques," writes Folkman in a recent issue of the Proceedings of the National Academy of Sciences.

The illustration shows an endothelial cell being shed from the vessel wall exposing tumor cells underneath. The researchers suggest this might be one model of mosaic vessel formation.

The paper's authors also suggest that their findings may explain the potency of some anti-cancer drugs currently in pre-clinical trials. They propose that the drugs may work by killing the tumor cells in mosaic vessels; this could damage the vessel and prevent blood flow to 14 percent of the tumor. Targeting vascular tumor cells may provide an additional weapon to fight cancer, says Munn.

These observations raise many questions. How do tumor cells actually invade blood vessels? Do mosaic blood vessels increase the chance of metastasis? Is drug delivery more efficient through these hybrid vessels? Are these vessels leaky? All of these questions represent future avenues of research, says Munn.

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Chang, Y. S. et al. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A 97, 14608-14613 (December 19, 2000).
Folkman, J. Can mosaic tumor vessels facilitate molecular diagnosis of cancer. Proc Natl Acad Sci U S A 98, 398-400 (January 16, 2001).

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