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Citations to this article

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis
Pallavi Chaturvedi, … , Andre Levchenko, Gregg L. Semenza
Pallavi Chaturvedi, … , Andre Levchenko, Gregg L. Semenza
Published December 17, 2012
Citation Information: J Clin Invest. 2013;123(1):189-205. https://doi.org/10.1172/JCI64993.
View: Text | PDF | Corrigendum
Research Article Article has an altmetric score of 17

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis

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Abstract

Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We demonstrate that HIFs mediate paracrine signaling between breast cancer cells (BCCs) and mesenchymal stem cells (MSCs) to promote metastasis. In a mouse orthotopic implantation model, MSCs were recruited to primary breast tumors and promoted BCC metastasis to LNs and lungs in a HIF-dependent manner. Coculture of MSCs with BCCs augmented HIF activity in BCCs. Additionally, coculture induced expression of the chemokine CXCL10 in MSCs and the cognate receptor CXCR3 in BCCs, which was augmented by hypoxia. CXCR3 expression was blocked in cocultures treated with neutralizing antibody against CXCL10. Conversely, CXCL10 expression was blocked in MSCs cocultured with BCCs that did not express CXCR3 or HIFs. MSC coculture did not enhance the metastasis of HIF-deficient BCCs. BCCs and MSCs expressed placental growth factor (PGF) and its cognate receptor VEGFR1, respectively, in a HIF-dependent manner, and CXCL10 expression by MSCs was dependent on PGF expression by BCCs. PGF promoted metastasis of BCCs and also facilitated homing of MSCs to tumors. Thus, HIFs mediate complex and bidirectional paracrine signaling between BCCs and MSCs that stimulates breast cancer metastasis.

Authors

Pallavi Chaturvedi, Daniele M. Gilkes, Carmen Chak Lui Wong, Kshitiz, Weibo Luo, Huafeng Zhang, Hong Wei, Naoharu Takano, Luana Schito, Andre Levchenko, Gregg L. Semenza

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 2 10 7 13 14 10 10 7 19 11 17 22 14 1 157
Citation information
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Citations to this article in year 2022 (13)

Title and authors Publication Year
Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment
R Lappano, L Todd, M Stanic, Q Cai, M Maggiolini, F Marincola, V Pietrobon
Cancers 2022
The Expression Pattern of Hypoxia-Related Genes Predicts the Prognosis and Mediates Drug Resistance in Colorectal Cancer
Y Yuan, L Tan, L Wang, D Zou, J Liu, X Lu, D Fu, G Wang, L Wang, Z Wang
Frontiers in Cell and Developmental Biology 2022
CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner
Xu Z, Gao H, Zhang Y, Feng W, Miao Y, Xu Z, Li W, Chen F, Lv Z, Huo J, Liu W, Shen X, Zong Y, Zhao J, Lu A
Molecular Therapy 2022
Mesenchymal/stromal stem cells: necessary factors in tumour progression
Li X, Fan Q, Peng X, Yang S, Wei S, Liu J, Yang L, Li H
Cell Death Discovery 2022
Glioblastoma‐educated mesenchymal stem‐like cells promote glioblastoma infiltration via extracellular matrix remodelling in the tumour microenvironment
Kim S, Lim E, Yoo K, Zhao Y, Kang J, Lim E, Shin I, Kang S, Lim HW, Lee S
Clinical and Translational Medicine 2022
CCL5 mediates breast cancer metastasis and prognosis through CCR5/Treg cells
Qiu J, Xu L, Zeng X, Wu H, Liang F, Lv Q, Du Z
Frontiers in Oncology 2022
Carcinoma-Associated Mesenchymal Stem/Stromal Cells: Architects of the Pro-tumorigenic Tumor Microenvironment
Frisbie L, Buckanovich RJ, Coffman L
STEM CELLS 2022
The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy
Kozal K, Krześlak A
Cancers 2022
Hypoxia-Inducible Expression of Annexin A6 Enhances the Resistance of Triple-Negative Breast Cancer Cells to EGFR and AR Antagonists
Williams SD, Smith TM, Stewart LV, Sakwe AM
Cells 2022
Targeting the tumor stroma for cancer therapy.
Xu M, Zhang T, Xia R, Wei Y, Wei X
Molecular Cancer 2022
Hypoxia-driven metabolic reprogramming of adipocytes fuels cancer cell proliferation.
Aird R, Wills J, Roby KF, Bénézech C, Stimson RH, Wabitsch M, Pollard JW, Finch A, Michailidou Z
Frontiers in Endocrinology 2022
Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids
Kozhukharova I, Minkevich N, Alekseenko L, Domnina A, Lyublinskaya O
International journal of molecular sciences 2022
Cell-Taxi: Mesenchymal Cells Carry and Transport Clusters of Cancer Cells
Zarubova J, Hasani-Sadrabadi MM, Norris SC, Majedi FS, Xiao C, Kasko AM, Li S
Small (Weinheim an Der Bergstrasse, Germany) 2022

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