4.3 Article

A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet β Cells

Journal

PANCREAS
Volume 50, Issue 7, Pages 982-989

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000001865

Keywords

rotary cell culture system; pancreatic ductal adenocarcinoma; MIN6; islets; 3D coculture; 3D; 3-dimensional; DM; diabetes mellitus; DMEM; Dulbecco's modified Eagle's medium; HARV; high aspect ratio vessel; IHC; immunohistochemistry; IGF; insulin-like growth factor; NAD; nonadherent dish; NOD; new-onset diabetes; PBS; phosphate-buffered saline; PDAC; pancreatic ductal adenocarcinoma; PI; pseudo islet; SEM; scanning electron microscopy; RCCS; rotary cell culture system; RPMI; Roswell Park Memorial Institute; T2DM; type 2 diabetes mellitus

Funding

  1. Pancreatic Cancer Research Fund

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By utilizing a rotary cell culture system, a simple in vitro 3D pancreatic model was established to study interactions between PDAC and islet beta cells. This system enabled the formation of 3D spheroids and showed PDAC cells' affinity to grow around and invade the pseudo islets, mimicking in vivo conditions.
Objectives To facilitate exploring a link between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus, we constructed a novel 3-dimensional (3D) in vitro coculturing system for studying interactions between PDAC and islet cells. Methods Adopting a 3D rotary cell culture system, we have cocultured several PDAC cell lines and MIN6 islet beta cells. The cellular morphology and viability of both cell types were investigated by time-lapse imaging, confocal and scanning electron microscopy, and immunohistochemistry. Results The developed coculture method enabled the formation of 3D PDAC and beta-cell spheroids (pseudo islets). We showed that surface morphology and growth of cultured cells mimicked their in vivo appearance. In addition, the coculture demonstrated the affinity of the PDAC cells to grow around and invade the pseudo islets. Conclusions Using rotary cell culture system, we have established a simple in vitro 3D pancreatic model. It is a flexible culture system that can easily be expanded with the addition of various stromal/neural components to further mimic in vivo conditions, thus enabling holistic investigation of the endocrine and exocrine pancreas.

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