Polyvinyl alcohol increased growth, migration, invasion, and sphere size in the PK-8 pancreatic ductal adenocarcinoma cell line

Fujiya Gomi; Norihiko Sasaki; Yuuki Shichi; Fuuka Minami; Seiichi Shinji; Masashi Toyoda; Toshiyuki Ishiwata

doi:10.1016/j.heliyon.2021.e06182

Polyvinyl alcohol increased growth, migration, invasion, and sphere size in the PK-8 pancreatic ductal adenocarcinoma cell line

Heliyon. 2021 Feb 4;7(2):e06182. doi: 10.1016/j.heliyon.2021.e06182. eCollection 2021 Feb.

Authors

Fujiya Gomi¹, Norihiko Sasaki², Yuuki Shichi¹, Fuuka Minami³, Seiichi Shinji^{1

4}, Masashi Toyoda², Toshiyuki Ishiwata¹

Affiliations

¹ Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
² Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
³ Department of Veterinary Pathology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
⁴ Departments of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8603, Japan.

Abstract

Polyvinyl alcohol (PVA) is a water-soluble synthetic polymer used in eye drops, embolization particles, and artificial cartilage. It has also been shown to cause expansion of functional multipotent self-renewing hematopoietic stem cells under serum-free conditions. In this study, we examined the effects of PVA on human pancreatic ductal adenocarcinoma (PDAC) cell lines using 2-dimensional (2D) and 3D-cultures with serum-free medium. In the 2D-culture, PVA-treatment induced an aggregated colony-like appearance in PDAC cells. It increased the growth of PK-8 cells in a dose-dependent manner as well as significantly increasing migration and invasion abilities. qRT-PCR showed an increase in α2 integrin and a decrease in matrix metalloprotease levels in PVA-treated PK-8 cells. Through qRT-PCR analysis, β1 integrin expression at the mRNA level was found to be decreased; however, it was unaltered at the protein level when assessed using FACS analysis. PVA further induced mesenchymal to epithelial transition-like alterations, including increased E-cadherin and decreased Vimentin and N-cadherin expression. Four cancer stem cell (CSC) markers were higher in PVA-treated PK-8 cells compared to controls. In 3D-culture, PVA-treated PK-8 cells showed a rod-like appearance with larger sphere size and higher growth ability. qRT-PCR showed that CSC markers did not increase and 2 of 4 drug transporters had decreased in PVA-treated PK-8 cells. These findings suggest that PVA increases the growth, migration, invasion, and sphere size of PK-8 cells, but does not increase the proportion of pancreatic CSCs under 3D-culture conditions with serum-free medium.

Keywords: Cancer stem cells; Invasion; Migration; Pancreatic cancer; Polyvinyl alcohol; Sphere.