神经生长因子是癌症治疗新靶点

xielirong

法国里尔大学Adriaenssens等的研究表明，以神经生长因子(NGF，神经营养因子之一)为靶点，可抑制乳腺癌细胞的增殖、存活和转移，故NGF是乳腺癌的潜在治疗靶点《癌症研究》（Cancer Research）。

研究者对一系列活检组织的分析表明，NGF在绝大多数人类乳腺肿瘤中都有广泛表达，抗NGF免疫反应主要集中在上皮性癌细胞。此外，在异种移植人类乳腺癌细胞的免疫缺陷鼠中也观察到，抗NGF抗体或抗NGF的小干扰RNA治疗可抑制肿瘤的生长和转移。这些直接以NGF为靶点的治疗在引起细胞增殖下降的同时，还可促进细胞凋亡和抑制肿瘤血管生成。

乳腺癌靶向治疗是分子水平的治疗方式，目前已有多种靶向药物应用于临床，神经生长因子在乳腺肿瘤的生长和转移过程中有其特定作用，有望成为新的靶向治疗靶点。




（Cancer Research），68, 346-351, January 15, 2008，Eric Adriaenssens, Hubert Hondermarck

Nerve Growth Factor Is a Potential Therapeutic Target in Breast Cancer
Eric Adriaenssens1, Elsa Vanhecke1, Pasquine Saule3, Alexandra Mougel3, Adeline Page2, Rodrigue Romon1, Victor Nurcombe4, Xuefen Le Bourhis1 and Hubert Hondermarck1

1 INSERM U908, Institut National de la Sante et de la Recherche Medicale, \"Growth factor signaling in breast cancer cells. Functional Proteomics\", IFR-147 and 2 Mass Spectrometry Facility, IFR-147, University Lille 1, 3 Centre National de la Recherche Scientifique UMR8527, Institute of Biology, Lille, France; and 4 Institute of Molecular and Cell Biology, Singapore, Singapore

Requests for reprints: Hubert Hondermarck, INSERM U908, Institut National de la Sante et de la Recherche Medicale, University Lille 1, Batiment SN3, 59655 Villeneuve d'Ascq, Lille, France. Phone: 33-320-43-40-97; E-mail: Hubert.hondermarck@univ-lille1.fr .


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. [Cancer Res 2008;68(2):346–51]