VEGFR1 has 2 roles in breast cancer--one angiogenic, one direct effect on bc cells

[Lani]

Dual Functional Role of VEGF Receptor in Breast Cancer Uncovered

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By Megan Rauscher

NEW YORK (Reuters Health) Oct 12 - The vascular endothelial growth factor receptor 1 (VEGFR-1) supports the growth and survival of breast cancer not only by inducing angiogenesis but also by activating VEGFR-1 on tumor cells, scientists report in a Fast Track paper in the October 1st International Journal of Cancer.

"The role of VEGFR-1 in the malignant process has been somewhat of a mystery," study investigator Dr. Daniel J. Hicklin from ImClone Systems Inc., New York, told Reuters Health.

Recent work at ImClone and elsewhere has shown that VEGFR-1 expression is upregulated on tumor vasculature and, "unexpectedly, on the tumor cells themselves," he explained.

In their latest studies, Dr. Hicklin and colleagues observed that specific inhibition of VEGFR-1 function, made possible by anti-VEGFR-1-specific neutralizing monoclonal antibodies, inhibited the growth of human breast cancer xenografts in mice.

This was accomplished, Dr. Hicklin said, "via a dual mechanism of targeting VEGFR-1 on tumor endothelium (anti-angiogenesis) and targeting VEGFR-1 directly on tumor cells (anti-tumor cell effects)."

"The anti-tumor effect was the result of reduced activation of MAPK or/and Akt in tumor cells resulting in reduced proliferation and increased apoptosis," the authors write.

This work, they say, "introduces the novel concept that antiangiogenic agents may target vascular and nonvascular targets" in breast cancer.

"The clinical implications of this work would be to treat patients with VEGFR-1 expressing cancers with a VEGFR-1-targeted agent," Dr. Hicklin said. "This would, to date, be a unique approach," he noted, adding that ImClone Systems is currently developing a VEGFR-1 antibody for clinical testing.

The expression of VEGFR-1 in breast tumors has recently been shown to be a significant prognostic indicator of poor outcome, high risk of metastasis and relapse, Dr. Hicklin and colleagues note in their report.

Int J Cancer 2006;119:1519-1529.



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