Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis
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Sharon Lim1, Kayoko Hosaka1, Masaki Nakamura1, Yihai Cao1,2,3,4
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden
2Department of Medical and Health Sciences, Linköping University, 581 83 Linköping, Sweden
3Affiliated WuXi No 2 Hospital of Nanjing Medical University, Wuxi 214 002, China
4Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK
Yihai Cao, e-mail: [email protected]
Keywords: adipose tissue, angiogenesis, tumor growth, vasculature, microenvironment
Received: March 23, 2016 Accepted: April 27, 2016 Published: May 18, 2016
Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth.
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