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Mol Oncol. 2015 Oct;9(8):1626-35. doi: 10.1016/j.molonc.2015.05.001. Epub 2015 May 14.

Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer.

Author information

1
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
2
Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia.
3
Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
4
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
5
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address: hubert.hondermarck@newcastle.edu.au.

Abstract

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.

KEYWORDS:

Breast cancer; Nerve fibers (axons); Nerve growth factor; Tumor microenvironment

PMID:
26009480
PMCID:
PMC5528785
DOI:
10.1016/j.molonc.2015.05.001
[Indexed for MEDLINE]
Free PMC Article

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