Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cellular functions modulated by endothelial cells in pancreatic cancer cells under hypoxic conditions

Pathol Res Pract. 2024 Mar:255:155192. doi: 10.1016/j.prp.2024.155192. Epub 2024 Feb 6.

Abstract

Background: In the tumor environment, malignant characteristics of cancer cells are promoted by stromal cells under hypoxia. It is unknown whether lysophosphatidic acid (LPA) receptor-mediated signaling is involved in the regulation of cellular functions by endothelial cells in pancreatic cancer cells under hypoxic conditions.

Methods: Pancreatic cancer (PANC-1) cells were co-cultured with endothelial (F2) cells and F2 cell supernatants at 21% and 1% O2. The Cell Culture Insert was used to assess the cell motile activity. The cell growth and viability to cisplatin (CDDP) were measured, using the Cell Counting Kit-8.

Results: LPA receptor expression levels were changed in PANC-1 cells co-cultured with F2 cells at 21% and 1% O2. The cell motile activities of PANC-1 cells co-cultured with F2 cells at 21% and 1% O2 were markedly elevated, compared with PANC-1 cells alone. The cell viabilities to CDDP of PANC-1 cells co-cultured with F2 cell supernatants at 21% and 1% O2 were regulated by the activation of LPA receptors.

Conclusion: These results suggest that LPA receptor-mediated signaling plays an important role in the modulation of pancreatic cancer cell functions by endothelial cells under hypoxic conditions.

Keywords: Endothelial cells; Hypoxia; LPA receptors; Lysophosphatidic acid; Pancreatic cancer cells.

MeSH terms

  • Cell Movement
  • Cisplatin / pharmacology
  • Endothelial Cells* / pathology
  • Humans
  • Hypoxia / metabolism
  • Lysophospholipids*
  • Pancreatic Neoplasms* / pathology
  • Receptors, Lysophosphatidic Acid / metabolism

Substances

  • lysophosphatidic acid
  • Receptors, Lysophosphatidic Acid
  • Cisplatin
  • Lysophospholipids