Research Papers:
CD47 deficiency in tumor stroma promotes tumor progression by enhancing angiogenesis
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Abstract
Lu Gao1, Kexin Chen1, Qi Gao1, Xiaodan Wang1, Jian Sun1, Yong-Guang Yang1,2
1The First Hospital and Institute of Immunology, Jilin University, Changchun, China
2Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA
Correspondence to:
Jian Sun, email: [email protected]
Yong-Guang Yang, email: [email protected]
Keywords: angiogenesis, CD47, SIRPα, TSP1, tumorigenesis
Received: April 11, 2016 Accepted: May 20, 2016 Published: June 07, 2016
ABSTRACT
CD47 is a transmembrane protein that functions as a receptor for thrombospondin-1 (TSP1) and a ligand for inhibitory receptor signal-regulatory protein-α (SIRPα). Blocking the interaction between CD47 on tumor cells and SIRPα on macrophages has been shown to induce antitumor responses. Here we investigated the role of CD47 expression in tumor stroma in tumorigenesis by comparing tumor growth in wild-type (WT) and CD47-deficient mice after subcutaneous injection of syngeneic prostate cancer cells. We found that CD47 deficiency in tumor stromal endothelial cells enhances angiogenesis, leading to suppressed tumor necrosis formation and accelerated tumor progression. Tumors from CD47-deficient mice also showed improved vascular integrity and stability, as well as increased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor 2 (VEGFR2) compared to those from WT mice. Moreover, reduced macrophage recruitment, likely due to decreased TSP1 production, was detected in tumors from CD47-deficient mice. Our results indicate that although treatment with antibody against CD47 induces antitumor immune responses by blocking the inhibitory CD47-SIRPα signaling, this treatment may also potentially promote tumor progression by blocking CD47 signaling in tumor stromal endothelial cells.
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PII: 9899