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Regulation of breast cancer extravasation by Angiopoietin‐1
Author(s) -
Harfouche Rania,
Hussain Sabah NA.,
Rabbani Shafaat A.,
Sengupta Shiladitya
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a254-b
Subject(s) - extravasation , breast cancer , medicine , cancer research , cancer cell , cancer , tumor necrosis factor alpha , metastasis , angiogenesis , angiopoietin receptor , inflammatory breast cancer , chemistry , pharmacology , immunology
The objective of this study was to investigate the roles of Angiopoietin‐1 (Ang‐1), a selective endothelial cell (EC) agonist, during breast cancer extravasation. We report for the first time that Ang‐1 modulates extravasation of metastatic breast cancer. We quantified breast cancer extravasation using a trans EC migration assay, where MDA‐MB‐231 cells were plated on a HUVEC monolayer which was pretreated with VEGF, TNF(or solvent. To determine the influence of Ang‐1 on breast cancer extravasation, either cell type was infected with Ang‐1 adenoviruses. Over expression of Ang‐1 in MDA‐MB‐231 cells potently inhibited their extravasation, both in the absence and presence of VEGF or TNF((p(0.05 vs Ad‐Fc‐infected control), an effect possibly mediated through the posttranslational phosphorylation of the MAPK pathway in ECs. Overexpression of Ang‐1 in HUVECs resulted in a significant reduction of MDA‐MB‐231 extravasation in the presence of TNF(or solvent. Interestingly, in contrast to MDA‐MB‐231 cells‐overexpressing Ang‐1, HUVEC‐derived Ang‐1 potentiated VEGF‐induced extravasation (p(0.05). We conclude that Ang‐1, mainly acting in a paracrine manner, is a potent inhibitor of breast cancer extravasation and counteracts the metastatic effects of VEGF and TNF(. Overexpressing Ang‐1 in breast cancer, rather than in endothelial, cells could hence be therapeutically beneficial for breast cancer patients.