Related Experiment Video
Updated: Jul 15, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
EDNRA-Expressing Mesenchymal Cells Are Expanded in Myeloma Interstitial Bone Marrow and Associated with Disease
Wen Ling1, Sarah K Johnson1, Syed J Mehdi1
1Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA.
Abstract:
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.
Insights
Endothelin receptor type A (EDNRA) is overexpressed in multiple myeloma (MM) bone marrow, increasing with disease progression. Elevated EDNRA marks dysfunctional vasculature and suggests a novel biomarker for MM progression and angiogenesis.
Area of Science:
- Oncology
- Cell Biology
- Vascular Biology
Background:
- Multiple myeloma (MM) disrupts the bone marrow (BM) microenvironment, causing mesenchymal cell dysfunction and promoting new blood vessel formation (neoangiogenesis).
- Pericytes and smooth muscle cells (SMCs) can detach from blood vessels and transform into cancer-associated fibroblasts within the MM microenvironment.
- Endothelin receptor type A (EDNRA), a marker for pericytes and SMCs, is found to be overexpressed in MM bone biopsies.
Purpose of the Study:
- To characterize the expression of EDNRA in the context of multiple myeloma.
- To investigate the correlation between EDNRA expression and MM disease progression and risk stratification.
- To identify the cellular origin and microenvironmental role of EDNRA-expressing cells in MM.
Main Methods:
- Analysis of EDNRA expression in whole MM bone biopsies.
- Correlation of EDNRA levels with MM disease stage, risk status, and focal lesion presence.
- Single-cell analysis of unexpanded BM mesenchymal cells.
- Immunohistochemistry to quantify EDNRA+ cells in interstitial BM and assess co-expression with other cellular markers.
Main Results:
- EDNRA expression progressively increased with MM disease advancement and was higher in high-risk patients.
- EDNRA expression was most elevated in MM focal lesions and associated with pericyte markers (RGS5, POSTN, CD146) and angiogenic marker FLT1.
- Single-cell analysis revealed EDNRA expression in a subset of mesenchymal cells with high proliferation gene expression.
- Immunohistochemistry confirmed an increase in interstitial EDNRA+ cells near MM growths, which coexpressed RGS5 and periostin, suggesting pericyte/SMC origin and detachment from angiogenic cells.
Conclusions:
- EDNRA is a novel microenvironmental biomarker in multiple myeloma.
- Increased presence of detached EDNRA-expressing cells indicates vascular disruption and heightened angiogenesis in MM.
- These findings highlight the role of pericyte/SMC-derived cells in the MM bone marrow pathology.
