Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0001511 (
Adhesion
)
5,955
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Differentiation of extravillous trophoblast cells (EVT) to an invasive phenotype plays an essential role in establishing and maintaining feto-placental organization during human pregnancy. A switch in integrin expression occurs during this differentiation and is accompanied by changes in the extracellular matrix (ECM). Alteration of EVT behavior is also modulated by cytokines. To investigate the molecular interactions involved in the EVT differentiation, we examined the effects of cytokines and ECM on the human EVT cell line,
TCL1
cells. We found that tumor necrosis factor alpha (TNFalpha) induced apoptosis in
TCL1
cells but not in JEG3 cells derived from choriocarcinoma while the addition of interleukin-1beta, leukemia inhibitory factor, or transforming growth factor had no effect on
TCL1
cells. This apoptosis was suppressed when
TCL1
cells were seeded on fibronectin (Fn), collagen type I (C1), collagen type IV (C4), or laminin (Ln). Wortmannin, a specific PI3 kinase inhibitor, inhibited this suppression. Spreading assays and adhesion blocking assays indicated that
TCL1
cells express integrin-alpha5 and -alpha6 and beta1 and beta4 subunits.
Adhesion
on Fn is mediated by alpha5beta1, and adhesion on C1, C4, or Ln is mediated by alpha6beta1 integrins. TNFalpha suppressed alpha6 integrin expression and enhanced alpha1 integrin expression in a dose-dependent manner. In addition, aggregation of beta1 subunits on C4 was detected after addition of TNFalpha. Taken together, these results suggest that TNFalpha and ECM, through activation of PI3 kinase mediated by beta1 integrin signaling, might collaboratively regulate differentiation of trophoblast cells through integrin signaling in establishing and maintaining successful pregnancy.
...
PMID:TNFalpha-induced apoptosis and integrin switching in human extravillous trophoblast cell line. 1260 73
