Tumor Blood Vessels Contain Multipotent Endothelial Cells

Cancer researchers have found that the cells making up the new blood vessels generated by rapidly growing tumors differ markedly from normal endothelial cells.

The concept of attacking tumors by preventing them from manufacturing new blood vessels (antiangiogenesis therapy) is not new. However, while this route has proven successful in some mouse models, the underlying premise has been that tumor-associated blood vessels were constructed from the same materials as normal blood vessels.

In the current report, investigators at Harvard Medical School (Cambridge, MA, USA) studied the genetic potential of the endothelial cells that line tumor blood vessels (TECs).

They reported in the September 2008 issue of the journal Cancer Cell that TECs were not mature endothelial cells, but rather were multipotent and had the potential to differentiate into both cartilage- and bone-like tissues. Differentiation into cartilage was accompanied by an activation of the cartilage-specific col2a1 and sox9 genes, whereas osteocalcin and the metastasis marker osteopontin were upregulated during differentiation into bone-like tissue.

"A primary assumption of antiangiogenesis therapy is that TECs are normal and derived from nearby, preexisting vessels," explained senior author Dr. Michael Klagsbrun professor of vascular biology at Harvard Medical School. "However, we and other groups have shown that there are several key differences between normal and tumor endothelium. These results suggest that TECs possess a stem/progenitor cell property that distinguishes them from ECs throughout the normal vasculature and undergo atypical differentiation."

Future studies will determine how the multipotent nature of the tumor vascular system is related to the development and spread of the tumor.

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