Premium
Inhibition of trophoblast invasion by the growth arrest‐specific 6 (Gas6) protein
Author(s) -
Mejia Camilo,
Johnston Andrew,
Lutz Rebecca,
Arroyo Juan,
Reynolds Paul
Publication year - 2015
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.29.1_supplement.684.10
Subject(s) - gas6 , trophoblast , receptor tyrosine kinase , syncytiotrophoblast , axl receptor tyrosine kinase , placenta , apoptosis , biology , andrology , receptor , downregulation and upregulation , cell growth , cancer research , microbiology and biotechnology , chemistry , endocrinology , medicine , signal transduction , pregnancy , fetus , biochemistry , jak stat signaling pathway , genetics , gene
Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure and decreased trophoblast invasion. The growth arrest‐specific 6 (Gas6) protein is known to induce different responses in cells including prevention of apoptosis and enhanced cell migration and invasion. This protein is secreted in response to growth arrest and it is increased during PE. Gas6 binds and induces signaling through the AXL receptor tyrosine kinase. Our objective was to identify expression of AXL in human control and PE placentas and to determine the role of Gas6 in trophoblast invasion as compared to cancer cells. Human control and PE placental samples were collected shortly after delivery. Tissues were frozen in liquid nitrogen for western blot studies or embedded for histological analysis. First trimester trophoblast cells were treated with Gas6 and invasion was measured using an xCELLigence RTCA DP (Real Time Cell Analysis Dual Plate) instrument. We observed: 1) AXL localization to the placental trophoblast cells; 2) decreased AXL expression in the syncytiotrophoblast of the PE placenta; 3) a 15% (p<0.05) decrease in trophoblast invasion after 24 hours of Gas6 treatment; and 4) a 36% increase (p<0.05) in cell invasion of A549 human adenocarcinoma cells after 24 hours of Gas6 treatment. We conclude that AXL receptor expression is decreased in the PE placenta and that Gas6 does not induce invasion in trophoblast cells. These results give insight into pathways associated with increased Gas6 observed during PE and could be useful in the clarifying potential mechanisms that orchestrate decreased trophoblast invasion in PE. (Supported by NIH grant 7K99HD055054‐02).