Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity-Reference-Cited by-全球学者库

Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity

Published:2024-01-19 Issue:3 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Zhou Hao¹²³^ORCID,Zhang Wenkan¹²³,Li Hengyuan²³⁴,Xu Fan⁵^ORCID,Yinwang Eloy¹²³,Xue Yucheng¹²³,Chen Tao¹²³^ORCID,Wang Shengdong¹²³,Wang Zenan¹²³^ORCID,Sun Hangxiang¹²³,Wang Fangqian¹²³,Mou Haochen¹²³,Yao Minjun¹²³,Chai Xupeng¹²³,Zhang Jiahao¹²³,Diarra Mohamed Diaty¹²³,Li Binghao²³⁴,Zhang Changqing⁶^ORCID,Gao Junjie⁶⁷^ORCID,Ye Zhaoming²³⁴^ORCID

Affiliation:

1. Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

2. Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.

3. Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China.

4. Department of Orthopedics, Musculoskeletal Tumor Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.

5. Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

6. Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

7. Shanghai Sixth People's Hospital Fujian, No. 16, Luoshan Section, Jinguang Road, Luoshan Street, Jinjiang City, Quanzhou, Fujian, China.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adi4298

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