Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening

T. J. Puls, Xiaohong Tan, Mahera Husain, Catherine F. Whittington, Melissa Fishel, Sherry L. Voytik-Harbin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.

Original languageEnglish (US)
Article number13039
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Preclinical Drug Evaluations
Neoplasms
Pancreatic Neoplasms
Phenotype
Collagen Type I
Fibroblasts
Cell Count
Clinical Trials
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening. / Puls, T. J.; Tan, Xiaohong; Husain, Mahera; Whittington, Catherine F.; Fishel, Melissa; Voytik-Harbin, Sherry L.

In: Scientific Reports, Vol. 8, No. 1, 13039, 01.12.2018.

Research output: Contribution to journalArticle

Puls, T. J. ; Tan, Xiaohong ; Husain, Mahera ; Whittington, Catherine F. ; Fishel, Melissa ; Voytik-Harbin, Sherry L. / Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{4bdb3187fd5446ae9e014c6728c80779,
title = "Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening",
abstract = "While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.",
author = "Puls, {T. J.} and Xiaohong Tan and Mahera Husain and Whittington, {Catherine F.} and Melissa Fishel and Voytik-Harbin, {Sherry L.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-31138-6",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening

AU - Puls, T. J.

AU - Tan, Xiaohong

AU - Husain, Mahera

AU - Whittington, Catherine F.

AU - Fishel, Melissa

AU - Voytik-Harbin, Sherry L.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.

AB - While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.

UR - http://www.scopus.com/inward/record.url?scp=85052701562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052701562&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-31138-6

DO - 10.1038/s41598-018-31138-6

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 13039

ER -