Background Information

: Excessive angiogenesis characterized by leaky, tortuous and chaotic vasculature is one of the hallmarks of cancers and is significantly correlated to poor prognosis. Disorganized angiogenesis leads to poor perfusion of anti-cancer drugs and limits access to immune cells. Hence, impeding angiogenesis is one of the attractive therapeutic targets to inhibit progression and metastasis in several solid tumors including breast.

Results

: We have developed a robust and reproducible method for isolating and ex vivo culture of endothelial cells derived from non-malignant (Endo-N) and malignant (Endo-T) part from clinically characterized human breast tumors. RT-PCR and immunoblotting analysis indicated that these cells exhibited expression of endothelial specific genes such as PECAM-1 (CD31), Endoglin (CD105), eNOS, VE-cadherin, VCAM1 and MCAM. Vasculogenic mimicry and contamination of progenitor endothelial cells recruited in tumors was ruled out by absence of CD133 expression and normal karyotype. Both the cell types showed stable expression of CD31 and CD105 up to seven passages. Furthermore, compared to Endo-N cells, Endo-T cells showed a) constitutively increased proliferation marked by nearly 36% of cells in mitotic phase, b) requirement of glutamine for cell survival, c) pro-migratory phenotype, d) produced increased number of sprouts in 3D cultures and e) resistance to sorafenib.

Conclusion

: Tumor derived endothelial cells showed distinct biological properties compared to normal breast endothelial cells.

Significance

: Our method for isolating endothelial cell types from human breast tumors may be explored to a) understand cellular and molecular mechanisms, b) screen anti-angiogenic molecules, and c) formulate organoid cultures to develop personalized medicine facilitating better clinical management of breast cancers.

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