Molecular mechanim of cancer-associated bone pain caused by protons

质子引起癌症相关骨痛的分子机制

• 批准号: 23390422
• 负责人: YONEDA Toshiyuki
• 金额: $ 12.31万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390422/
• 关键词: 口腔生化学; プロトン; 骨痛; 骨転移

Bone pain is one of the most common complications associated with bone metastasis. It causes increased morbidity and undermining QOL in cancer patients with bone metastasis. However, the molecular basis of bone pain remains unclear. We reasoned that acidic conditions contribute to bone pain, because cancer creates acidic extracellular microenvironment and acid is a well-known algesic substance.We found that extracellular microenvironment of bone-colonizing cancer was acidic due to proton release via V-ATPase proton pump expressed on plasma membrane. Microarray analysis using primary sensory neuron cells isolated from dorsal root ganglions (DRG) demonstrated that acidic microenvironment increased the transcription of several genes including CGRP and Snap25.Our findings suggest that acidic microenvironments created by cancer cells colonizing bone contribute to elicitation of bone pain through regulating the expression of algogenic genes in DRG sensory neurons.

骨痛是骨转移瘤最常见的并发症之一。它会导致癌症骨转移患者的发病率增加和生活质量下降。然而，骨痛的分子基础仍不清楚。我们推断，酸性条件有助于骨痛，因为癌症创造酸性细胞外微环境，酸是众所周知的痛觉物质。我们发现，骨定植癌的细胞外微环境是酸性的，这是由于通过质膜上表达的V-ATP酶质子泵释放质子。采用背根神经节（DRG）原代感觉神经元细胞进行的微阵列分析显示，酸性微环境可增加CGRP和Snap 25等基因的转录，提示癌细胞在骨内定植所产生的酸性微环境通过调节DRG感觉神经元致痛基因的表达而参与骨痛的诱发。

项目成果

The De ubiquitinating Enzyme USP45 Is Critical to Epithelial-mesenchymal Transition (EMT) in Breast Cancer Cells Colonized Bone

去泛素化酶 USP45 对于乳腺癌细胞定植骨中的上皮-间质转化 (EMT) 至关重要

• 发表时间: 2012
• 作者: Tanaka S;Yoneda T
• 通讯作者: Yoneda T

Bone pain associated with cancer metastasis to bone. Plenary lecture at ANZBMS/ JSBMR Joint Meeting and IOF Regionals

与癌症骨转移相关的骨痛。

• 发表时间: 2011
• 作者: Nakata;M.;Kimura;K. R.;Sumitomo;T.;Wada;S.;Sugauchi;A.;Oki;E.;Higashino;M.;Kreikemeyer;B.;Podbielski;A.;Okahashi;N.;Hamada;S.;Isoda;R.;Terao;Y.;and Kawabata;S;Yoneda T
• 通讯作者: Yoneda T

Crosstalk between metastatic cancer cells and bone microenvironment

转移性癌细胞与骨微环境之间的串扰

• 发表时间: 2011
• 作者: Kimura KR;Nakata M;Sumitomo T;Kreikemeyer B;Podbielski A;Terao Y;and Kawabata S;Yoneda T
• 通讯作者: Yoneda T

Molecular events involved in bone pain

骨痛涉及的分子事件

• 发表时间: 2011
• 作者: 谷村明彦;根津顕弘;森田貴雄;斎藤一郎;Yoneda T
• 通讯作者: Yoneda T

骨微小環境と癌

骨微环境与癌症

• 发表时间: 2012
• 作者: Soichi Tanaka;Kenji Hata;Toshiyuki Yoneda;米田俊之
• 通讯作者: 米田俊之