Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity

被引：16

作者：

Zhou, Hao ^{[1
,2
,3
]}

Zhang, Wenkan ^{[1
,2
,3
]}

Li, Hengyuan ^{[2
,3
,4
]}

Xu, Fan ^{[5
]}

Yinwang, Eloy ^{[1
,2
,3
]}

Xue, Yucheng ^{[1
,2
,3
]}

Chen, Tao ^{[1
,2
,3
]}

Wang, Shengdong ^{[1
,2
,3
]}

Wang, Zenan ^{[1
,2
,3
]}

Sun, Hangxiang ^{[1
,2
,3
]}

Wang, Fangqian ^{[1
,2
,3
]}

Mou, Haochen ^{[1
,2
,3
]}

Yao, Minjun ^{[1
,2
,3
]}

Chai, Xupeng ^{[1
,2
,3
]}

Zhang, Jiahao ^{[1
,2
,3
]}

Diarra, Mohamed Diaty ^{[1
,2
,3
]}

Li, Binghao ^{[2
,3
,4
]}

Zhang, Changqing ^{[6
]}

Gao, Junjie ^{[6
,7
]}

Ye, Zhaoming ^{[2
,3
,4
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthoped Surg, Hangzhou, Zhejiang, Peoples R China

[2] Zhejiang Univ, Orthoped Res Inst, Hangzhou, Zhejiang, Peoples R China

[3] Key Lab Motor Syst Dis Res & Precis Therapy Zhejia, Hangzhou, Zhejiang, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 2, Musculoskeletal Tumor Ctr, Sch Med, Hangzhou 310009, Peoples R China

[5] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Dermatol, Hangzhou, Zhejiang, Peoples R China

[6] Shanghai Jiao Tong Univ, Dept Orthoped, Shanghai Peoples Hosp 6, Sch Med, Shanghai, Peoples R China

[7] Shanghai Sixth Peoples Hosp Fujian, 16 Luoshan Sect,Jinguang Rd,Luoshan St, Quanzhou, Fujian, Peoples R China

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 03期

基金：

中国国家自然科学基金;

关键词：

BREAST-CANCER GROWTH; STROMAL CELLS; BONE; TRANSPORT; EXPRESSION; PROTECTS; ABLATION; PROMOTE; DNA;

D O I：

10.1126/sciadv.adi4298

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Bone is one of the most common sites of tumor metastases. During the last step of bone metastasis, cancer cells colonize and disrupt the bone matrix, which is maintained mainly by osteocytes, the most abundant cells in the bone microenvironment. However, the role of osteocytes in bone metastasis is still unclear. Here, we demonstrated that osteocytes transfer mitochondria to metastatic cancer cells and trigger the cGAS/STING-mediated antitumor response. Blocking the transfer of mitochondria by specifically knocking out mitochondrial Rho GTPase 1 (Rhot1) or mitochondrial mitofusin 2 (Mfn2) in osteocytes impaired tumor immunogenicity and consequently resulted in the progression of metastatic cancer toward the bone matrix. These findings reveal the protective role of osteocytes against cancer metastasis by transferring mitochondria to cancer cells and potentially offer a valuable therapeutic strategy for preventing bone metastasis.

引用

页数：16

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