Back to Search
Start Over
Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain
- Source :
- PLoS ONE, PLoS ONE, Vol 5, Iss 4, p e10234 (2010)
- Publication Year :
- 2010
- Publisher :
- Public Library of Science, 2010.
-
Abstract
- BACKGROUND: There is current interest in understanding the molecular mechanisms of tumor-induced bone pain. Accumulated evidence shows that endogenous formaldehyde concentrations are elevated in the blood or urine of patients with breast, prostate or bladder cancer. These cancers are frequently associated with cancer pain especially after bone metastasis. It is well known that transient receptor potential vanilloid receptor 1 (TRPV1) participates in cancer pain. The present study aims to demonstrate that the tumor tissue-derived endogenous formaldehyde induces bone cancer pain via TRPV1 activation under tumor acidic environment. METHODOLOGY/PRINCIPAL FINDINGS: Endogenous formaldehyde concentration increased significantly in the cultured breast cancer cell lines in vitro, in the bone marrow of breast MRMT-1 bone cancer pain model in rats and in tissues from breast cancer and lung cancer patients in vivo. Low concentrations (1 approximately 5 mM) of formaldehyde induced pain responses in rat via TRPV1 and this pain response could be significantly enhanced by pH 6.0 (mimicking the acidic tumor microenvironment). Formaldehyde at low concentrations (1 mM to 100 mM) induced a concentration-dependent increase of [Ca(2+)]i in the freshly isolated rat dorsal root ganglion neurons and TRPV1-transfected CHO cells. Furthermore, electrophysiological experiments showed that low concentration formaldehyde-elicited TRPV1 currents could be significantly potentiated by low pH (6.0). TRPV1 antagonists and formaldehyde scavengers attenuated bone cancer pain responses. CONCLUSIONS/SIGNIFICANCE: Our data suggest that cancer tissues directly secrete endogenous formaldehyde, and this formaldehyde at low concentration induces metastatic bone cancer pain through TRPV1 activation especially under tumor acidic environment.
- Subjects :
- Male
Pathology
medicine.medical_specialty
TRPV1
lcsh:Medicine
Pain
TRPV Cation Channels
Bone Neoplasms
Breast Neoplasms
CHO Cells
Prostate cancer
Breast cancer
Cricetulus
Anesthesiology and Pain Management/Chronic Pain Management
Cricetinae
Formaldehyde
medicine
Animals
Humans
lcsh:Science
Bone pain
Anesthesiology and Pain Management
Multidisciplinary
Bone cancer
business.industry
Neuroscience/Sensory Systems
lcsh:R
Cancer
Bone metastasis
Prostatic Neoplasms
medicine.disease
Rats
medicine.anatomical_structure
Urinary Bladder Neoplasms
Anesthesiology and Pain Management/Acute Pain Management
Cancer research
lcsh:Q
Female
Bone marrow
medicine.symptom
business
Acids
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....9068569540e085e76931cb619c022b08