Nerve growth factor links oral cancer progression, pain, and cachexia

Yi Ye, Dongmin Dang, Jianan Zhang, Chi T. Viet, David K. Lam, John C. Dolan, Jennifer Gibbs, Brian Schmidt

Research output: Contribution to journalArticle

Abstract

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms.

Original languageEnglish (US)
Pages (from-to)1667-1676
Number of pages10
JournalMolecular Cancer Therapeutics
Volume10
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Cachexia
Mouth Neoplasms
Nerve Growth Factor
Neoplasms
Pain
Cytokines
Inflammation
Weight Loss
Nociception
Cancer Pain
Leptin
Squamous Cell Carcinoma
Cell Culture Techniques
Quality of Life

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nerve growth factor links oral cancer progression, pain, and cachexia. / Ye, Yi; Dang, Dongmin; Zhang, Jianan; Viet, Chi T.; Lam, David K.; Dolan, John C.; Gibbs, Jennifer; Schmidt, Brian.

In: Molecular Cancer Therapeutics, Vol. 10, No. 9, 09.2011, p. 1667-1676.

Research output: Contribution to journalArticle

Ye, Yi ; Dang, Dongmin ; Zhang, Jianan ; Viet, Chi T. ; Lam, David K. ; Dolan, John C. ; Gibbs, Jennifer ; Schmidt, Brian. / Nerve growth factor links oral cancer progression, pain, and cachexia. In: Molecular Cancer Therapeutics. 2011 ; Vol. 10, No. 9. pp. 1667-1676.
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