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

Scientific Reports
T J PulsSherry L Voytik-Harbin

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 tumo...Continue Reading

References

May 2, 2003·Nature Reviews. Cancer·Peter Friedl, Katarina Wolf
Dec 28, 2006·BMC Medicine·Paolo P ProvenzanoPatricia J Keely
Jan 30, 2008·Birth Defects Research. Part C, Embryo Today : Reviews·Milan Makale
Oct 11, 2008·Fundamental & Clinical Pharmacology·G Y Perret, M Crépin
Nov 26, 2009·Cell·Kandice R LeventalValerie M Weaver
Mar 30, 2010·Trends in Biotechnology·Fabian ZanellaWolfgang Link
Apr 27, 2010·Pancreas·Emily L DeerSean J Mulvihill
Apr 16, 2011·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Nemil ShahHyunki Kim
Nov 29, 2011·Cell·Peter Friedl, Stephanie Alexander
Dec 20, 2011·Critical Reviews in Oncology/hematology·Shawn P CareyCynthia A Reinhart-King
Jun 20, 2012·Essays in Biochemistry·Mitsuo Yamauchi, Marnisa Sricholpech
Sep 4, 2012·Mutation Research·Nina KramerHelmut Dolznig
Oct 2, 2012·Molecular Cancer Research : MCR·George S KaragiannisEleftherios P Diamandis
Dec 15, 2012·Critical Reviews in Oncogenesis·Clifford WhatcottDaniel D Von Hoff
Feb 5, 2013·Molecular Cancer Research : MCR·Daniele M GilkesGregg L Semenza
Mar 26, 2013·Journal of Cell Science·Marta CanelValerie G Brunton
Jul 10, 2013·Cancer Chemotherapy and Pharmacology·Salaheldin S HamedWilliam J Jusko
Jul 31, 2013·Current Opinion in Cell Biology·Stephanie AlexanderPeter Friedl
Nov 10, 2013·Nature Medicine·Daniela F Quail, Johanna A Joyce
Mar 13, 2014·Advanced Drug Delivery Reviews·Anna Astashkina, David W Grainger
Apr 8, 2014·Cancer Discovery·Carlo ToniattiGiulio Draetta
Apr 15, 2014·Biofabrication·Chengyang WangWei Sun
Jun 7, 2014·Frontiers in Pharmacology·John C Dawson, Neil O Carragher
Dec 17, 2014·American Journal of Physiology. Cell Physiology·Shawn P CareyCynthia A Reinhart-King
Feb 11, 2015·The Journal of Clinical Investigation·Yulong ChenJonathan M Kurie
Feb 20, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Clifford J WhatcottHaiyong Han
Feb 25, 2015·Trends in Biotechnology·Ruchi MalikEdna Cukierman
Jun 21, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lindsay E Clegg, Feilim Mac Gabhann
Jun 26, 2015·Science Translational Medicine·Fabien VincentMarie-Claire Peakman

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Citations

Sep 4, 2020·Micromachines·Lexi L CrowellTayloria N G Adams
May 3, 2020·Journal of Experimental & Clinical Cancer Research : CR·Somshuvra BhattacharyaPilar de la Puente
Sep 16, 2020·Cancer Metastasis Reviews·Michael W LeeAnna Capasso
Apr 25, 2020·Frontiers in Bioengineering and Biotechnology·Kristina V KitaevaValeriya V Solovyeva
Oct 7, 2020·Brain : a Journal of Neurology·Polyxeni NikolakopoulouAnna Herland
Feb 4, 2021·F1000Research·Yael ParanZvi Kam
Jan 24, 2021·Drug Discovery Today·Sophia Malandraki-Miller, Paul R Riley
Feb 23, 2021·Lab on a Chip·Bisan SamaraMohammad A Qasaimeh
Oct 10, 2020·Progress in Biophysics and Molecular Biology·Lars H Wegner, Zhifeng Hao
Jul 27, 2021·Current Opinion in Biomedical Engineering·Della S Shin, Kristi S Anseth
Sep 22, 2021·Journal of Molecular Biology·Shalaka PatilKundan Sengupta
Nov 26, 2021·Advanced Drug Delivery Reviews·Thomas J DePalmaAleksander Skardal

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Methods Mentioned

BETA
xenograft
confocal microscopy

Software Mentioned

Perkin
Oligomer
Harmony
GraphPad Prism
GraphPad
Imaris

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