Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain

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	Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain
	Tong, Zhiqian ; Luo, Wenhong ; Wang, Yanqing ; Yang, Fei ; Han, Ying ; Li, Hui ; Luo, Hongjun ; Duan, Bo ; Xu, Tianle(徐天乐） ; Maoying, Qiliang ; Tan, Huangying ; Wang, Jun ; Zhao, Hongmei ; Liu, Fengyu ; Wan, You
刊名	PLOS ONE
	2010
卷号	5 期号:4 页码:e10234-e10235
关键词	DORSAL-ROOT GANGLION COMPLETE FREUNDS-ADJUVANT ISOLATED RAT HEPATOCYTES HUMAN OSTEOBLASTIC CELLS BREAST-CANCER CAPSAICIN RECEPTOR ION-CHANNEL GLUTATHIONE EXPRESSION MELATONIN
ISSN号	1932-6203
通讯作者	Tong, ZQ (reprint author), Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China,tzq88666883@sina.com
英文摘要	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 similar to 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.
学科主题	Life Sciences & Biomedicine - Other Topics
收录类别	SCI
资助信息	National Natural Science Foundation of China[30700206, 30800332]; Ministry of Education of China[B07001]; National Basic Research Program of the Ministry of Science and Technology of China[2007CB512501]; Key Project of Chinese Ministry of Education[109003]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1598]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Tong, Zhiqian,Luo, Wenhong,Wang, Yanqing,et al. Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain[J]. PLOS ONE,2010,5(4):e10234-e10235.
APA	Tong, Zhiqian.,Luo, Wenhong.,Wang, Yanqing.,Yang, Fei.,Han, Ying.,...&Wan, You.(2010).Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain.PLOS ONE,5(4),e10234-e10235.
MLA	Tong, Zhiqian,et al."Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain".PLOS ONE 5.4(2010):e10234-e10235.