Effect of bacterial contamination in bile on pancreatic cancer cell survival

Hannah R Shrader; Ann M Miller; Ann Tomanek-Chalkley; Ashley McCarthy; Kristen L Coleman; Po Hien Ear; Ashutosh K Mangalam; Aliasger K Salem; Carlos H F Chan

doi:10.1016/j.surg.2020.09.029

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Effect of bacterial contamination in bile on pancreatic cancer cell survival

Journal article

Peer reviewed

Effect of bacterial contamination in bile on pancreatic cancer cell survival

Hannah R Shrader, Ann M Miller, Ann Tomanek-Chalkley, Ashley McCarthy, Kristen L Coleman, Po Hien Ear, Ashutosh K Mangalam, Aliasger K Salem and Carlos H F Chan

Surgery, Vol.169(3), pp.617-622

03/2021

DOI: 10.1016/j.surg.2020.09.029

PMCID: PMC7870517

PMID: 33268071

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Abstract

Introduction of gut ﬂora into the biliary system is common owing to biliary stenting in patients with obstructing pancreatic head cancer. We hypothesize that alteration of biliary microbiome modiﬁes bile content that modulates pancreatic cancer cell survival. Human bile samples were collected during pancreaticoduodenectomy. Bacterial strains were isolated from contaminated (stented) bile and identiﬁed using 16S ribosomal RNA sequencing. Human pancreatic cancer cells (AsPC1, CFPAC, Panc1) were treated for 24 hours with sterile (nonstented) bile, contaminated (stented) bile, and sterile bile preincubated with 10 colony forming unit of live bacteria isolated from contaminated bile or a panel of bile acids for 24 hours at 37°C, and evaluated using CellTiter-Blue Cell Viability Assay (Promega Corp. Madison, WI). Human bile (30-50 μl/mouse) was coinjected intraperitoneally with 10 Panc02 mouse pancreatic cancer cells in C57BL6/N mice to evaluate the impact of bile on peritoneal metastasis 3 to 4 weeks after tumor challenge. While all bile samples signiﬁcantly reduced peritoneal metastasis of Panc02 cells in mice, some contaminated bile samples had diminished antitumor effect. All sterile bile (n = 4) reduced pancreatic cancer cell survival in vitro. Only 40% (2/5) of contaminated bile samples had significant effect. Preincubation of sterile bile with live Enterococcus faecalis or Streptococcus oralis modified the antitumor effect of sterile bile. These changes were not observed with culture media preincubated with live bacteria, suggesting live gut bacteria can modify the antitumor components present in bile. Conjugated bile acids were more potent than unconjugated cholic acid in reducing pancreatic cancer cell survival. Alteration of bile microbiome from biliary stenting has a direct impact on pancreatic cancer cell survival. Further study is warranted to determine if this microbiome shift alters tumor microenvironment.

Cell Survival - drug effects

Bile Acids and Salts - pharmacology

Bacterial Infections - etiology

Humans

Pancreatic Neoplasms - surgery

Male

Surgical Wound Infection - etiology

Pancreaticoduodenectomy - adverse effects

Pancreaticoduodenectomy - methods

Dose-Response Relationship, Drug

Animals

Gastrointestinal Microbiome - drug effects

Heterografts

Cell Line, Tumor

Bile - microbiology

Female

Mice

Pancreatic Neoplasms - mortality

Pancreatic Neoplasms - complications

Disease Models, Animal

Details

Title: Subtitle: Effect of bacterial contamination in bile on pancreatic cancer cell survival
Creators: Hannah R Shrader - Department of Surgery, University of Iowa, Iowa City, IA
Ann M Miller - Department of Surgery, University of Iowa, Iowa City, IA
Ann Tomanek-Chalkley - Department of Surgery, University of Iowa, Iowa City, IA
Ashley McCarthy - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Kristen L Coleman - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Po Hien Ear - Department of Surgery, University of Iowa, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Ashutosh K Mangalam - Department of Pathology, University of Iowa, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Carlos H F Chan - Department of Surgery, University of Iowa, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA. Electronic address: carloshfchan@gmail.com
Resource Type: Journal article
Publication Details: Surgery, Vol.169(3), pp.617-622
DOI: 10.1016/j.surg.2020.09.029
PMID: 33268071
PMCID: PMC7870517
NLM abbreviation: Surgery
ISSN: 0039-6060
eISSN: 1532-7361
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS T32 CA078586 / NCI NIH HHS
Language: English
Date published: 03/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Pathology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Holden Comprehensive Cancer Center
Record Identifier: 9984070143702771

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