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Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1highCD206+ pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis.
Zhou, Jing; Song, Qing; Li, Haoze; Han, Yicun; Pu, Yunzhou; Li, Ling; Rong, Wenqing; Liu, Xiaodie; Wang, Ziyuan; Sun, Jian; Song, Yuqing; Hu, Xueyan; Zhu, Guanghao; Zhu, Huirong; Yang, Liu; Ge, Guangbo; Li, Hongshan; Ji, Qing.
Afiliación
  • Zhou J; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Song Q; Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang, 315010, China.
  • Li H; Department of Medical Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangsu, 215007, China.
  • Han Y; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Pu Y; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Li L; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Rong W; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Liu X; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Wang Z; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Sun J; Department of Pathology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Song Y; Department of Peripheral Vascular Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Hu X; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Zhu G; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Zhu H; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Yang L; Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Ge G; Department of Oncology, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. bsyykyc@shutcm.edu.cn.
  • Li H; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. geguangbo@shutcm.edu.cn.
  • Ji Q; Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang, 315010, China. lihongshan_1982@126.com.
Mol Cancer ; 23(1): 168, 2024 Aug 20.
Article en En | MEDLINE | ID: mdl-39164758
ABSTRACT

BACKGROUND:

Information transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM.

METHODS:

We utilized qPCR and FISH to measure circRNAs expression levels in human CRC plasma, primary CRC tissues, and liver metastatic tissues. Additionally, we employed immunofluorescence, RNA sequencing, and in vivo experiments to assess the effect mechanism of circ-0034880-enriched TEVs on PMN formation and CRC metastasis. DARTS, CETSA and computational docking modeling were applied to explore the pharmacological effects of Ginsenoside Rb1 in impeding PMN formation.

RESULTS:

We found that circ-0034880 was highly enriched in plasma extracellular vesicles (EVs) derived from CRC patients and closely associated with CRLM. Functionally, circ-0034880-enriched TEVs entered the liver tissues and were absorbed by macrophages in the liver through bloodstream. Mechanically, TEVs-released circ-0034880 enhanced the activation of SPP1highCD206+ pro-tumor macrophages, reshaping the metastasis-supportive host stromal microenvironment and promoting overt metastasis. Importantly, our mechanistic findings led us to discover that the natural product Ginsenoside Rb1 impeded the activation of SPP1highCD206+ pro-tumor macrophages by reducing circ-0034880 biogenesis, thereby suppressing PMN formation and inhibiting CRLM.

CONCLUSIONS:

Circ-0034880-enriched TEVs facilitate strong interaction between primary tumor cells and SPP1highCD206+ pro-tumor macrophages, promoting PMN formation and CRLM. These findings suggest the potential of using Ginsenoside Rb1 as an alternative therapeutic agent to reshape PMN formation and prevent CRLM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Osteopontina / Vesículas Extracelulares / ARN Circular / Neoplasias Hepáticas Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Osteopontina / Vesículas Extracelulares / ARN Circular / Neoplasias Hepáticas Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido