Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids

Jie Zheng, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Boshi Sun, Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, United States.Follow
Domenica Berardi, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Lingeng Lu, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Hong Yan, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Shujian Zheng, Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, United States.
Oladimeji Aladelokun, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Yangzhouyun Xie, Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, United States.
Yujun Cai, Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, United States.
Krystal J. Godri Pollitt, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow
Sajid A. Khan, Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, United States.Follow
Caroline H. Johnson, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Connecticut 06510, United States.Follow

Document Type

Article

Publication Title

Environmental science & technology

Abstract

Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants that are of increasing public concern worldwide. However, their relationship with colorectal cancer (CRC) is poorly understood. This study aims to comprehensively investigate the effect of PFOS and PFOA on the development and progression of CRC in vitro using a series of biological techniques and metabolic profiling. Herein, the migration of three-dimensional (3D) spheroids of two CRC cell lines, SW48 KRAS wide-type (WT) and SW48 KRAS G12A, were observed after exposure to PFOS and PFOA at 2 μM and 10 μM for 7 days. The time and dose-dependent migration phenotype induced by 10 μM PFOS and PFOA was further confirmed by wound healing and trans-well migration assays. To investigate the mechanism of action, derivatization-mass spectrometry-based metabolic profiles were examined from 3D spheroids of SW48 cell lines exposed to PFOS and PFOA (2 μM and 10 μM). Our findings revealed this exposure altered epithelial-mesenchymal transition related metabolic pathways, including fatty acid β-oxidation and synthesis of proteins, nucleotides, and lipids. Furthermore, this phenotype was confirmed by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. These findings show novel insight into the relationship between PFOS, PFOA, and CRC.

First Page

21016

Last Page

21028

DOI

10.1021/acs.est.3c04844

Publication Date

12-19-2023

Identifier

38064429 (pubmed); 10.1021/acs.est.3c04844 (doi)

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