BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Journal of Experimental & Clinical Cancer Research : CR
Marie OuarnéSabine Bailly

Abstract

Angiogenesis has become an attractive target for cancer therapy. However, despite the initial success of anti-VEGF (Vascular endothelial growth factor) therapies, the overall survival appears only modestly improved and resistance to therapy often develops. Other anti-angiogenic targets are thus urgently needed. The predominant expression of the type I BMP (bone morphogenetic protein) receptor ALK1 (activin receptor-like kinase 1) in endothelial cells makes it an attractive target, and phase I/II trials are currently being conducted. ALK1 binds with strong affinity to two ligands that belong to the TGF-ß family, BMP9 and BMP10. In the present work, we addressed their specific roles in tumor angiogenesis, cancer development and metastasis in a mammary cancer model. For this, we used knockout (KO) mice for BMP9 (constitutive Gdf2-deficient), for BMP10 (inducible Bmp10-deficient) and double KO mice (Gdf2 and Bmp10) in a syngeneic immunocompetent orthotopic mouse model of spontaneous metastatic breast cancer (E0771). Our studies demonstrate a specific role for BMP9 in the E0771 mammary carcinoma model. Gdf2 deletion increased tumor growth while inhibiting vessel maturation and tumor perfusion. Gdf2 deletion also increased the number...Continue Reading

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Citations

Jul 6, 2019·Growth Factors·Lap Hing ChiRobin L Anderson
Feb 12, 2020·Oncogene·Claire ViallardBruno Larrivée
May 22, 2021·Molecular and Cellular Biochemistry·Qian-Qian JiangKe-Shu Xu
Jul 10, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Agnès Desroches-CastanSabine Bailly
Sep 2, 2021·Chinese Neurosurgical Journal·Haishuang TangQiao Zuo

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Methods Mentioned

BETA
FCS
PCR
ELISAs
ELISA

Software Mentioned

Axiovision
GraphPad Prism6
Zen Blue
ImageJ

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