Back to Search
Start Over
Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy
- Source :
- Oncotarget
- Publication Year :
- 2014
- Publisher :
- Impact Journals, LLC, 2014.
-
Abstract
- // Wen Wen Xu 1, 2 , Bin Li 1, 2, 3 , Alfred KY Lam 4 , Sai Wah Tsao 1, 3 , Simon YK Law 3, 5 , Kwok Wah Chan 2, 3, 6 , Qiu Ju Yuan 1 , Annie LM Cheung 1, 2, 3 1 Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China 2 The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI), China 3 Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China 4 Department of Pathology, Griffith Medical School and Griffith Health Institute, Gold Coast Campus, Gold Coast, QLD 4222, Australia 5 Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China 6 Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China Correspondence to: Annie LM Cheung, e-mail: lmcheung@hku.hk Keywords: Tumor angiogenesis, Bone marrow-derived cells, Tumor microenvironment, VEGF receptors, Antibody therapy Received: September 18, 2014 Accepted: November 19, 2014 Published: December 17, 2014 ABSTRACT Increasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1 + and VEGFR2 + bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1 + or VEGFR2 + non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1 + and VEGFR2 + non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.
- Subjects :
- Male
Oncology
medicine.medical_specialty
animal structures
Esophageal Neoplasms
Angiogenesis
Mice, Nude
Tumor angiogenesis
Metastasis
Mice
Internal medicine
Animals
Humans
Medicine
Molecular Targeted Therapy
VEGF receptors
Neoplasm Staging
Tumor microenvironment
Vascular Endothelial Growth Factor Receptor-1
Tissue microarray
Neovascularization, Pathologic
business.industry
respiratory system
Esophageal cancer
medicine.disease
Antibodies, Neutralizing
Immunohistochemistry
Vascular Endothelial Growth Factor Receptor-2
Xenograft Model Antitumor Assays
Blockade
body regions
medicine.anatomical_structure
Immunology
Cancer cell
cardiovascular system
Female
Antibody therapy
Bone marrow
Bone marrow-derived cells
business
circulatory and respiratory physiology
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....87bc48558967c5b906cb09df91fad159