Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Rasoulzadeh, Z; Ghods, R; Kazemi, T; Mirzadegan, E; Ghaffari-Tabrizi-Wizsy, N; Rezania, S; Kazemnejad, S; Arefi, S; Ghasemi, J; Vafaei, S; Mahmoudi, AR; Zarnani, AH.
Placental Kisspeptins Differentially Modulate Vital Parameters of Estrogen Receptor-Positive and -Negative Breast Cancer Cells.
PLoS One. 2016; 11(4):e0153684-e0153684 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Ghaffari Tabrizi-Wizsy Nassim
Rezania Simin
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Number of Figures: 7
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Abstract:
Kisspeptins (KPs) are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC) metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM) significantly reduced proliferation of both cell types compared to CM without (w/o) KP (CM-w/o KP) in a dose- and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2-30 hr), while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and -negative BC cells possibly through modulation of pro-inflammatory cytokine production.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Apoptosis -
Blotting, Western -
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Movement -
Cell Proliferation -
Female -
Humans -
Immunoenzyme Techniques -
Immunoprecipitation -
Kisspeptins - genetics
Kisspeptins - metabolism
Placenta - metabolism
Pregnancy -
RNA, Messenger - genetics
Real-Time Polymerase Chain Reaction -
Receptors, Estrogen - genetics
Receptors, Estrogen - metabolism
Reverse Transcriptase Polymerase Chain Reaction -
Tumor Cells, Cultured -
Wound Healing -
Young Adult -

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