Synergistic effects of multiple myeloma cells and tumor-associated macrophages on vascular endothelial cells in vitro
- PDF / 11,151,314 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 36 Downloads / 199 Views
ORIGINAL PAPER
Synergistic effects of multiple myeloma cells and tumor‑associated macrophages on vascular endothelial cells in vitro Miaomiao Sun1 · Sen Qiu2 · Qiankun Xiao1 · Tong Wang1 · Xiangyu Tian1 · Chao Chen1 · Xiaohui Wang4 · Junya Han1 · Haina Zheng1 · Yuwei Shou1 · Kuisheng Chen1,3 Received: 4 June 2020 / Accepted: 26 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Angiogenesis is a prerequisite for multiple myeloma development. Tumor cells can stimulate angiogenesis by secreting vascular endothelial growth factor A (VEGFA), but we previously reported that tumor angiogenesis was not significantly reduced when VEGFA expression was inhibited in myeloma cells. Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment and have been reported to be involved in the regulation of angiogenesis. In this study, we performed in vitro macrophage coculture studies and studies with RPMI 8226 and TAMs cell-conditioned media to explore their effects on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Our results showed that M2 macrophages and RPMI 8226 cells could synergistically promote HUVEC proliferation, migration, and tube formation, and that VEGFA depletion in both cell types suppressed HUVEC tube formation ability. Conversely, M1 macrophages inhibited the tube formation in HUVECs. Mechanistically, M2 macrophage secretion of VEGFA may affect vascular endothelial growth factor receptor 1 signaling to regulate angiogenesis. In summary, our results suggest that macrophage clearance or inducing of transformation of M2 macrophages into M1 macrophages are potential treatment strategies for multiple myeloma. Keywords Multiple myeloma · Tumor-associated macrophage · Vascular endothelial growth factor A · M2 macrophage · Angiogenesis
Introduction
Miaomiao Sun, Sen Qiu: Co first authors. * Kuisheng Chen [email protected] 1
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Dong Road, Zhengzhou 450000, Henan, People’s Republic of China
2
Department of Pathology, People’s Hospital of Zhengzhou, No.33 Huanghe Road, Zhengzhou 450003, Henan, People’s Republic of China
3
Henan Province Key Laboratory of Tumor Pathology, Department of Pathology of The First Affiliated Hospital of Zhengzhou University, No.40 Daxue Road, Zhengzhou 450003, Henan, People’s Republic of China
4
Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiankang Road, XinXiang 453000, Henan, People’s Republic of China
Multiple myeloma (MM), the second-most common hematologic malignancy, is a plasma cell dyscrasia [1]. In recent decades, through the development and application of various drugs, the median survival period of patients with MM has been greatly extended. However, existing treatment options are still not ideal, and the disease cannot be completely cured because of the development of drug resistance [2]. Tumor an
Data Loading...
