Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells

Roxanne L. Massoumi, Yaroslav Teper, Soichiro Ako, Linda Ye, Elena Wang, O. Joe Hines, Guido Eibl

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood. Methods The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting. Results The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 =5-fold) in AsPC-1 and 2584 genes (339 =5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt. Conclusions The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.

Original languageEnglish
Pages (from-to)524-528
Number of pages5
JournalPancreas
Volume50
Issue number4
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

  • RNA-seq
  • lipopolysaccharide
  • obesity
  • pancreatic cancer

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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