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Remodeling of tumor microenvironment by extracellular matrix protein 1a differentially regulates ovarian cancer metastasis.
Yu, Yinjue; Lyu, Cuiting; Li, Xiaojing; Yang, Lina; Wang, Jingshu; Li, Hui; Xin, Zhaochen; Xu, Xinyi; Ren, Chunxia; Yang, Gong.
Afiliación
  • Yu Y; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China; Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • Lyu C; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Li X; Department of Pathology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Yang L; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Wang J; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Li H; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Xin Z; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Xu X; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China; Department of Pathology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China.
  • Ren C; Center for Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: renchunxia2018@shutcm.edu.cn.
  • Yang G; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200140, China; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, 200032, China. Electronic address:
Cancer Lett ; 596: 217022, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38849014
ABSTRACT
We previously reported that extracellular matrix protein 1 isoform a (ECM1a) promotes epithelial ovarian cancer (EOC) through autocrine signaling by binding to cell surface receptors αXß2. However, the role of ECM1a as a secretory molecule in the tumor microenvironment is rarely reported. In this study, we constructed murine Ecm1-knockout mice and human ECM1a-knockin mice and further generated orthotopic or peritoneal xenograft tumor models to mimic the different metastatic stages of EOC. We show that ECM1a induces oncogenic metastasis of orthotopic xenograft tumors, but inhibits early-metastasis of peritoneal xenograft tumors. ECM1a remodels extracellular matrices (ECM) and promotes remote metastases by recruiting and transforming bone marrow mesenchymal stem cells (BMSCs) into platelet-derived growth factor receptor beta (PDGFRß+) cancer-associated fibroblasts (CAFs) and facilitating the secretion of angiopoietin-like protein 2 (ANGPTL2). Competing with ECM1a, ANGPTL2 also binds to integrin αX through the P1/P2 peptides, resulting in negative effects on BMSC differentiation. Collectively, this study reveals the dual functions of ECM1a in remodeling of TME during tumor progression, emphasizing the complexity of EOC phenotypic heterogeneity and metastasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Proteínas de la Matriz Extracelular / Ratones Noqueados / Microambiente Tumoral / Fibroblastos Asociados al Cáncer / Proteína 2 Similar a la Angiopoyetina Límite: Animals / Female / Humans Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Proteínas de la Matriz Extracelular / Ratones Noqueados / Microambiente Tumoral / Fibroblastos Asociados al Cáncer / Proteína 2 Similar a la Angiopoyetina Límite: Animals / Female / Humans Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda