Transforming growth factor β1 alters calcium mobilizing properties and endogenous ATP release in A549 cells: Possible implications for cell migration

Kenji Miki, Hiromitsu Tanaka, Yoko Nagai, Chiwaka Kimura, Masahiro Oike

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9 Citations (Scopus)

Abstract

We examined the effects of transforming growth factor β1 (TGFβ1) on cellular functions in human lung cancer cell line A549. Treatment of A549 cells with 1 ng/ml TGFβ1 for more than 3 days altered their morphology from an epithelial cobblestone-like appearance to a fibroblastlike one, reduced the expression of E-cadherin mRNA and protein, and induced the formation of F-actin fibers. These hallmarks indicate that TGFβ1 induced the epithelial-mesenchymal transition in A549 cells. Migration of TGFβ1-treated A549 cells, which was quantified by the wound-healing assay, was markedly accelerated by 3 μ M ATPγS, a non-hydrolyzable ATP analogue. ATPγSinduced migration of TGFβ1-treated A549 cells was reversed by the P2 antagonist suramin. In contrast, migration of control A549 cells was not altered by ATPγS. TGFβ1-treated A549 cells showed an augmentation of ATP-induced Ca2+ transients, thapsigargin-induced Ca2+ transients, and store-operated Ca2+ entry compared with those in control cells. Basal level of the extracellular ATP concentration was significantly lower in TGFβ1-treated A549 cells than in control cells. We conclude from these results that TGFβ1 augments ATP-induced Ca2+ mobilization, which leads to the acceleration of migration, in A549 cells but, it markedly reduces endogenous ATP release. This implies that the actions of ATP would become a novel therapeutic target for inhibiting cancer cell migration.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalJournal of Pharmacological Sciences
Volume113
Issue number4
DOIs
Publication statusPublished - Jul 23 2010

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Transforming Growth Factors
Cell Movement
Adenosine Triphosphate
Calcium
A549 Cells
Suramin
Thapsigargin
Epithelial-Mesenchymal Transition
Cadherins
Wound Healing
Actins
Lung Neoplasms
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Transforming growth factor β1 alters calcium mobilizing properties and endogenous ATP release in A549 cells : Possible implications for cell migration. / Miki, Kenji; Tanaka, Hiromitsu; Nagai, Yoko; Kimura, Chiwaka; Oike, Masahiro.

In: Journal of Pharmacological Sciences, Vol. 113, No. 4, 23.07.2010, p. 387-394.

Research output: Contribution to journalArticle

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