title: Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties.
abstract: Poor survival rates from lung cancer can largely be attributed to metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME) is composed of multiple cell types, as well as non-cellular components. The TME plays a critical role in the development of metastatic cancers by providing migratory cues and changing the properties of the tumor cells. The Extracellular Matrix (ECM), a main component of the TME, has been shown to change composition during tumor progression, contributing to cancer cell invasion and survival away from the primary cancer site. Although the ECM is well-known to influence the fate of tumor progression, little is known about the molecular mechanisms that are affected by the cancer cell-ECM interactions. It is imperative that these mechanisms are elucidated in order to properly understand and prevent lung cancer dissemination. However, common in vitro studies do not incorporate these interactions into everyday cell culture assays. We have adopted a model that examines decellularized human fibroblast-derived ECM as a 3-dimensional substrate for growth of lung adenocarcinoma cell lines. Here, we have characterized the effect of fibroblast-derived matrices on the properties of various lung-derived epithelial cell lines, including cancerous and non-transformed cells. This work highlights the significance of the cell-ECM interaction and its requirement for incorporation into in vitro experiments. Implementation of a fibroblast-derived ECM as an in vitro technique will provide researchers with an important factor to manipulate to better recreate and study the TME.
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Bioengineering, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Scherzer
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Sabine
authors.initials: S
authors.lastname: Waigel
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Medicine, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Howard
authors.initials: H
authors.lastname: Donninger
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Vennila
authors.initials: V
authors.lastname: Arumugam
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Medicine, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zacharias
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Clark
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Siskind
authors.affiliation: Department of Bioengineering, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Soucy
authors.affiliation: J. G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Bioengineering, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Medicine, University of Louisville, Louisville, Kentucky, 40202, United States of America; Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, 40202, United States of America.
authors.forename: Levi
authors.initials: L
authors.lastname: Beverly
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D059016:Tumor Microenvironment