Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis

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. ; Funding Agencies|Swedish Research Council; Swedish Cancer Foundation; Karolinska Institute Foundation; Karolinska Institute; Torsten Soderbergs foundation; European Research Council (ERC) advanced grant ANGIOFAT [250021]; Knut Alice Wallenberg Foundation; Novo Nordisk Foundation; Alex and Eva Wallstroms foundation; Lars Hiertas Minne foundation