Involvement of LPA receptor-5 in the enhancement of cell motile activity by phorbol ester and anticancer drug treatments in melanoma A375 cells

• Published in: Biochemical and biophysical research communications Vol. 496; no. 1; pp. 225 - 230
• Main Authors: Fukushima, Kaori, Takahashi, Kaede, Kurokawa, Aya, Ishimoto, Kaichi, Otagaki, Shiho, Minami, Kanako, Fukushima, Nobuyuki, Honoki, Kanya, Tsujiuchi, Toshifumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29-01-2018
• Subjects: 60 APPLIED LIFE SCIENCES; ACETATES; Anticancer drug; ANTINEOPLASTIC DRUGS; Cell motility; GENES; LPA5; Melanoma cells; MELANOMAS; Phorbol ester; PHORBOL ESTERS; RECEPTORS; Cell motility; Anticancer drug; PDBu; CDDP; TPA; Phorbol ester; Melanoma cells; DTIC; LPA5; LPA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.01.030

Lysophosphatidic acid (LPA) signaling through six subtypes of LPA receptors (LPA1 to LPA6) regulates a variety of biological responses in cancer cells. The aim of our study was to evaluate an involvement of LPA receptors in the activation of cell motility by phorbol ester and anticancer drug treatments in melanoma A375 cells. Cells were treated with 12-O-tetradecanoylphorbol- 13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu) for 3 days. The cell motile activity of TPA treated cells was significantly higher than that of PDBu treated cells, correlating with LPAR5 expression levels. LPA5 knockdown suppressed the high cell motile activity induced by TPA. To assess whether the cell motile activity of A375 cells is stimulated through LPA5 induced by anticancer drugs, the long-term cisplatin (CDDP) and dacarbazine (DTIC) treated cells were generated from A375 cells (A375-CDDP and A375-DTIC cells, respectively). The expression levels of LPA receptor genes were changed in A375-CDDP and A375-DTIC cells. In particular, CDDP and DTIC treatment markedly elevated LPAR5 expressions. The cell motile activities of A375-CDDP and A375-DTIC cells were significantly higher than that of untreated cells. These results suggest that the cell motile activity is regulated through the induction of LPA5 by phorbol ester and anticancer drug treatments in A375 cells.
•The cell motility and LPAR5 gene expression was increased by TPA in melanoma A375 cell.•The high cell motile activity of TPA treated cells was suppressed by LPA5 knockdown.•The cell motility of A375 cells was stimulated by the long-term CDDP and DTIC treatment.•LPAR5 gene expression was markedly elevated in the long-term CDDP and DTIC treated cells. .•LPA5 is involved in the activation of cell motility by phorbol esters and anticancer drugs in A375 cells.