Transforming Growth Factor β1 Alters Calcium Mobilizing Properties and Endogenous ATP Release in A549 Cells: Possible Implications for Cell Migration

Journal of Pharmacological Sciences

Chiwaka Kimura¹  Kenji Miki¹  Hiromitsu Tanaka¹  Masahiro Oike¹  Yoko Nagai¹ 

[1] Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Japan

关键词: A549 cell;    store-operated calcium entry;    P2 receptor;    cell migration;    epithelial–mesenchymal transition;   

DOI  :  10.1254/jphs.10124FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(35)Cited-By(8)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 fibroblast-like 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 μM ATPγS, a non-hydrolyzable ATP analogue. ATPγS-induced 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.

【 授权许可】

Unknown