Oxytocin induces proliferation and migration in immortalized human dermal microvascular endothelial cells and human breast tumor-derived endothelial cells.
Oxytocin either increases or inhibits cell growth in different cell subtypes. We tested here the effect of oxytocin on cell proliferation and migration of human dermal microvascular endothelial cells (HMEC) and tumor-associated endothelial cells purified from human breast carcinomas (B-TEC). Oxytocin receptors were expressed in both cell subtypes at mRNA and protein levels. Through oxytocin receptor, oxytocin (1 nmol/L-1 mumol/L) significantly increased cell proliferation and migration in both HMEC and B-TEC, and addition of a selective oxytocin antagonist fully reverted these effects. To verify whether a different expression of adhesion molecule-related genes could be responsible for the oxytocin-induced cell migration, untreated and treated cells were compared applying a microarray technique. In HMEC, oxytocin induced the overexpression of the matrix metalloproteinase (MMP)-17, cathepsin D, and integrin beta(6) genes. In B-TEC, oxytocin significantly switched on the gene profile of some MMP (MMP-11 and MMP-26) and of integrin beta(6). The up-regulation of the integrin beta(6) gene could be involved in the oxytocin-induced cell growth, because this subunit is known to determine activation of mitogen-activated protein kinase-extracellular signal-regulated kinase 2, which is involved in the oxytocin mitogenic effect. In B-TEC, oxytocin also increased the expression of caveolin-1 at gene and protein levels. Because oxytocin receptor localization within caveolin-1-enriched membrane domains is necessary for activation of the proliferative (instead of the inhibitory) response to oxytocin, its enhanced expression can be involved in the oxytocin-induced B-TEC growth as well. Altogether, these data indicate that oxytocin contributes to cell motility and growth in HMEC and B-TEC.
Cassoni
Paola
P
Department of Biomedical Sciences and Oncology, University of Turin, Italy. paola.cassoni@unito.it
Marrocco
Tiziana
T
Bussolati
Benedetta
B
Allia
Elena
E
Munaron
Luca
L
Sapino
Anna
A
Bussolati
Gianni
G
D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002402:Cathepsin D / Q000235:genetics; D051242:Caveolin 1 / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply
D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; D018045:Receptors, Oxytocin; C072170:integrin beta6; D010121:Oxytocin; D002402:Cathepsin D; D020782:Matrix Metalloproteinases; D002118:Calcium