15P - Adipose tissue vascular promotes tumor growth rate and metastasis
|Date||17 December 2016|
|Event||ESMO Asia 2016 Congress|
|Topics|| Basic Science
|Citation||Annals of Oncology (2016) 27 (suppl_9): ix1-ix8. 10.1093/annonc/mdw573|
Many different types of cancer occur in adipose tissue environment that is highly vascularized. However, the role of adipose pre-existing vascular bed on tumor growth, angiogenesis and metastasis is unknown. Here, we report that pre-existing vascular density in adipose tissue environment is crucial for tumor takeoff, growth, angiogenesis and metastasis.
EO771, B16 and T241 cell lines were implanted in the subcutaneous dorsal, white adipose tissue (WAT) or brown adipose tissue (BAT) of C57BL/6 mice. Tumor sizes were measured throughout each experiment. Tumor tissues were dissected, fixed in PFA, followed by whole mount staining or immunohistochemical staining to investigate blood vessels density (CD31), pericytes (NG2) coverage and perfusion (Dextran).
Implantation of 3 different cell lines including breast cancer, melanoma and fibrosarcoma into the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) demonstrated that the rate of tumor take off, tumor angiogenesis and growth, and metastasis are dependent on the degree of pre-existing vascularization in these tissues. Tumor cells implanted in the BAT and WAT grew significantly faster than tumor cells implanted in the subcutaneous tissue. In addition, tumor cells implanted in the adipose tissues have increased neovascularization and blood perfusion, and their vasculatures are poorly coated with perivascular cell coverage resulting in increased leakage.
Thus, our study shows that adipose vasculature predetermines the tumor microenvironment that supports tumor growth and progression.
Clinical trial indentification
No clinical trial involved
Legal entity responsible for the study
The Swedish Research Council; the Swedish Cancer Foundation; the Karolinska Institute Foundation; the Karolinska Institute distinguished professor award; the Torsten Soderbergs foundation; the European Research Council (ERC) advanced grant ANGIOFAT (Project no 250021); the Knut Alice Wallenberg Foundation; the Novo Nordisk Foundation for the advanced grant; the Alex and Eva Wallströms foundation and the Lars Hiertas Minne foundation.
All authors have declared no conflicts of interest.