Scientists identify cells necessary for tumor an...( e necessary to support and sustain tumo...)

In this study, Id-deficient mice were transplanted with bone marrow cells from donor wild-type mice (normal mice) that were marked with a protein (B-galactosidase+), which allows them to turn blue when stained with a specific dye. Four weeks later, these mice were injected with either lymphoma cells or Lewis Lung Carcinoma cells (lung cancer cell lines). The transplanted mice developed widespread metastasis and died within 26 days, paralleling the tumor growth observed in wild-type animals.

Importantly, the blue bone marrow derived cells were seen in the vast majority of the vessels formed in the tumors. When the reverse experiment was done - putting Id-deficient marrow back into wild-type mice - there was a dramatic delay in the growth of the tumor. This showed that the bone marrow-derived cells could promote the formation of new blood vessels by tumors and may also be required for their formation.

"This is the first definitive proof that bone marrow contributes to the formation of functional blood vessels of certain tumors," said Dr. Shahin Rafii, one of the study's senior authors. "It increases our understanding of the mechanism by which anti-angiogenic agents block tumor growth, generating new targets for cancer therapy."

These findings raised the issue of which specific cells in the bone marrow are responsible for early angiogenesis. To determine this, the researchers tracked the bone marrow cells labeled with B-galactosidase+. A few days after the engraftment, bone marrow cells identified as circulating endothelial precursor cells by the blue enzymatic reaction to B-galactosidase+ became incorporated into the lining of tumor blood vessel cells. These cells expressed one of the VEGF receptors, VEGFR 2 that is critical for growth and survival of these cells. An unexpected finding was that hematopoietic precursor cells were also found to contribute to the formation of the blood ves
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Contact: Joanne Nicholas
nicholaj@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
31-Oct-2001