Modulation of chemoresistance by lysophosphatidic acid (LPA) signaling through LPA5 in melanoma cells treated with anticancer drugs

Kanako Minami; Nanami Ueda; Haruka Maeda; Kaichi Ishimoto; Shiho Otagaki; Toshifumi Tsujiuchi

doi:10.1016/j.bbrc.2019.07.092

Modulation of chemoresistance by lysophosphatidic acid (LPA) signaling through LPA₅ in melanoma cells treated with anticancer drugs

Biochem Biophys Res Commun. 2019 Sep 17;517(2):359-363. doi: 10.1016/j.bbrc.2019.07.092. Epub 2019 Jul 27.

Authors

Kanako Minami¹, Nanami Ueda¹, Haruka Maeda¹, Kaichi Ishimoto¹, Shiho Otagaki¹, Toshifumi Tsujiuchi²

Affiliations

¹ Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
² Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan. Electronic address: ttujiuch@life.kindai.ac.jp.

PMID: 31362892
DOI: 10.1016/j.bbrc.2019.07.092

Abstract

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA₁ to LPA₆) contributes to the promotion of malignant potency in cancer cells. The cell motile activity are stimulated through the induction of LPA₅ in melanoma cells treated with anticancer drugs. The present study aimed to investigate whether LPA signaling via LPA₅ regulates chemoresistance in melanoma A375 cells. Cells were treated with cisplatin (CDDP) or dacarbazine (DTIC) every 24 h for 2 days. CDDP and DTIC treatment increased LPAR5 expressions. The cell survival rates of A375 cells treated with CDDP and DTIC were significantly decreased by LPA. In addition, LPAR5 expression was markedly elevated in long-term CDDP treated (A375-CDDP) cells. LPA decreased the cell survival rate of A375-CDDP cells treated with CDDP. To evaluate the roles of LPA₅ in chemoresistance during tumor progression, highly migratory (A375-R11) cells were established from A375 cells. LPAR5 expression level was significantly lower in A375-R11 cells than in A375 cells. The cell survival rates of A375-R11 cells treated with CDDP and DTIC were increased, compared with A375 cells. Moreover, we generated LPA₅ knockdown cells from A375 cells. The cell survival rates of A375 cells treated with CDDP and DTIC were significantly elevated by LPA₅ knockdown. These results suggest that LPA signaling via LPA₅ is involved in the modulation of chemoresistance in melanoma A375 cells.

Keywords: Anticancer drug; Chemoresistance; LPA; LPA(5); Melanoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Survival / drug effects
Cisplatin / pharmacology*
Dacarbazine / pharmacology*
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Humans
Lysophospholipids / metabolism*
Melanoma / drug therapy*
Melanoma / genetics
Melanoma / metabolism
Receptors, Lysophosphatidic Acid / genetics
Receptors, Lysophosphatidic Acid / metabolism*
Signal Transduction / drug effects

Substances

Antineoplastic Agents
LPAR5 protein, human
Lysophospholipids
Receptors, Lysophosphatidic Acid
Dacarbazine
lysophosphatidic acid
Cisplatin