Corticosteroids and medroxyprogesterone acetate inhibit the induction of E-selectin on the vascular endothelium by MDA-MB-231 breast cancer cells.
The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between breast cancer cells and vascular endothelial cells in the expression of E-selectin, and the effect of corticosteroids or medroxyprogesterone acetate (MPA) on such interaction. An MDA-MB-231 cell line, derived from human breast cancer induced E-selectin on the cell surface of human umbilical vascular endothelial cells. This induction was enhanced with a supplement of mononuclear cells of peripheral blood added to the culture medium. Corticosteroids and MPA blocked the induction of E-selectin proportional to concentration. Anti-IL-1 beta, but not anti-IL1 alpha or- TNF a, antibodies blocked induction. These findings suggest that MDA-MB-231 cells induce expression of E-selectin on vascular endothelium by releasing IL-1 beta directly or indirectly, but this induction is blocked by corticosteroids and MPA. Corticosteroids and MPA may inhibit cancer metastasis by blocking E-selectin expression on the vascular endothelium.
Narita
T
T
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Kawakami-Kimura
N
N
Matsuura
N
N
Hosono
J
J
Kannagi
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D001685:Biological Factors; D019040:E-Selectin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D017258:Medroxyprogesterone Acetate