Nerve growth factor is a potential therapeutic target in breast cancer.
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.
Adriaenssens
Eric
E
INSERM U908, Institut National de la Sante et de la Recherche Medicale, University Lille 1, Lille, France.
Vanhecke
Elsa
E
Saule
Pasquine
P
Mougel
Alexandra
A
Page
Adeline
A
Romon
Rodrigue
R
Nurcombe
Victor
V
Le Bourhis
Xuefen
X
Hondermarck
Hubert
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020932:Nerve Growth Factor