The endothelin axis stimulates the expression of pro-inflammatory cytokines and pro-migratory molecules in breast cancer.
We investigated the effects of the endothelin-1 (ET-1) receptor dual antagonist (Bosentan®) on the inflammatory cytokines and the chemoattractant molecules associated with breast cancer growth and the development of tumor infiltration in bone explants. Immunocompetent mice implanted with the murine mammary carcinoma 4T1 cells in a skin-fold chamber and treated with Bosentan® had reduced tumor growth (p < .05). ET-1 promoted the secretion of the anti-inflammatory soluble tumor necrosis factor (TNF) receptor and IL12 p40 in vitro. The Bosentan® treatment in vivo was associated with a local increase of the anti-inflammatory IL-1α cytokine concentration and decrease of the pro-inflammatory TNF-α and IL-17 cytokine concentrations (p < .05).
Jewell
Ashley N
AN
Department of Biology, University of North Carolina—Charlotte, USA.
Swamydas
Muthulekha
M
Castillo
Claudia I
CI
Wyan
Heather
H
Allen
Lauren D
LD
McDermott
Kerri A
KA
Eddy
Jill M
JM
Dréau
Didier
D
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D000077300:Bosentan; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D017466:Receptors, Endothelin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000959:Antihypertensive Agents; D016207:Cytokines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D018836:Inflammation Mediators; D020381:Interleukin-17; D053582:Interleukin-1alpha; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000077300:Bosentan