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EDNRA-Expressing Mesenchymal Cells Are Expanded in Myeloma Interstitial Bone Marrow and Associated with Disease Progression.
Ling, Wen; Johnson, Sarah K; Mehdi, Syed J; Alapat, Daisy V; Bauer, Michael; Zangari, Maurizio; Schinke, Carolina; Thanendrarajan, Sharmilan; van Rhee, Frits; Yaccoby, Shmuel.
Afiliación
  • Ling W; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Johnson SK; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Mehdi SJ; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Alapat DV; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Bauer M; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Zangari M; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Schinke C; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Thanendrarajan S; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • van Rhee F; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
  • Yaccoby S; Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
Cancers (Basel) ; 15(18)2023 Sep 12.
Article en En | MEDLINE | ID: mdl-37760488
Multiple myeloma (MM) induces dysfunctional bone marrow (BM) mesenchymal cells and neoangiogenesis. Pericytes and smooth muscle cells (SMCs) could detach from vessels and become cancer-associated fibroblasts. We found that the pericyte and SMC marker endothelin receptor type A (EDNRA) is overexpressed in whole MM bone biopsies; we sought to characterize its expression. EDNRA expression gradually increased with disease progression. High-risk MM patients had higher EDNRA expression than low-risk MM patients and EDNRA expression was highest in focal lesions. High EDNRA expression was associated with high expression of pericyte markers (e.g., RGS5, POSTN, and CD146) and the angiogenic marker FLT1. A single-cell analysis of unexpanded BM mesenchymal cells detected EDNRA expression in a subset of cells that coexpressed mesenchymal cell markers and had higher expression of proliferation genes. Immunohistochemistry revealed that the number of EDNRA+ cells in the interstitial BM increased as MM progressed; EDNRA+ cells were prevalent in areas near the MM focal growth. EDNRA+ cells were detached from CD34+ angiogenic cells and coexpressed RGS5 and periostin. Therefore, they likely originated from pericytes or SMCs. These findings identify a novel microenvironmental biomarker in MM and suggest that the presence of detached EDNRA+ cells indicates disrupted vasculature and increased angiogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza