Cellular responses to low nutrient conditions via activation of lysophosphatidic acid (LPA) receptor signaling in gastric cancer cells

Abstract

In the center of the solid tumor, abnormal vascular architecture impedes sufficient blood supply, leading to continuous hypoxia and nutrient deprivation for the tumor cells. Lysophosphatidic acid (LPA) receptor signaling is known to drive a range of malignant behaviors in cancer cells. This study aimed to explore the impact of LPA receptors on cellular functions in gastric cancer AGS cells cultured under low nutrient conditions. When AGS cells were cultured in media containing low glucose (2000 mg/L), low glutamine (1 mM), or low amino acids (50 % content), LPA receptor expression levels were significantly altered. The growth activity of AGS cells cultured in low glucose- and low amino acid-containing media was suppressed by LPA. Conversely, LPA increased the growth activity of AGS cells cultured in low glutamine-containing media. AGS cell motility increased under low glucose and low glutamine conditions, while low amino acid conditions decreased cell motility. Additionally, the viability of AGS cells in response to cisplatin (CDDP) was enhanced under low glucose, low glutamine, and low amino acid conditions. The motility and viability of AGS cells in response to CDDP were significantly increased by AM966 (LPA₁ antagonist), GRI-977143 (LPA₂ agonist) and (2S)-OMPT (LPA₃ agonist). These results suggest that LPA receptor signaling is significantly implicated in regulating malignant properties in AGS cells under low nutrient conditions.