Abstract
We show here that nerve growth factor (NGF), the prototypic neurotrophin, can be targeted in breast cancer to inhibit tumor cell proliferation, survival, and metastasis. Analysis of a series of biopsies revealed widespread expression of NGF in the majority of human breast tumors, with anti-NGF immunoreactivity concentrated in the epithelial cancer cells. Moreover, immunodeficient mice xenografted with human breast cancer cells and treated with either anti-NGF antibodies or small interfering RNA against NGF displayed inhibited tumor growth and metastasis. Such treatments directed against NGF induced a decrease in cell proliferation with a concomitant increase in apoptosis of breast cancer cells and an inhibition of tumor angiogenesis. Together, these data indicate that targeting NGF in breast cancer may have therapeutic ramifications.
Highlights
Despite considerable progress in both the diagnosis and treatment, breast cancer remains the second leading cause of cancer deaths among women
It has previously been shown that nerve growth factor (NGF), the first isolated neurotrophin well-known for its role in nervous system development, is able to stimulate the in vitro growth and survival of breast cancer cells through its activation of the tyrosine kinase receptor TrkA and the death receptor p75NTR [2,3,4,5]
We investigated NGF expression in human breast tumor biopsies and applied anti-NGF treatments to immunodeficient mice xenografted with human breast cancer cells
Summary
Despite considerable progress in both the diagnosis and treatment, breast cancer remains the second leading cause of cancer deaths among women. The multifactorial nature of breast carcinogenesis, as well as the cellular and molecular diversity within tumors, have rendered difficult for the development of molecularly targeted treatments that can be applied to the broad range of breast tumors. This is well-illustrated with the protooncogenic tyrosine kinase membrane receptor Erb-B2 and its corresponding peptidic drug Herceptin [1]; Herceptin has proven to be a very efficient antibreast cancer drug, the fact that only 20% of breast cancers overexpress Erb-B2 is a limitation to its wider use in therapy. These in vitro effects of NGF on breast cancer cells, and the fact
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