Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties

• Published in: PloS one Vol. 10; no. 9; p. e0138065
• Main Authors: Scherzer, Michael T, Waigel, Sabine, Donninger, Howard, Arumugam, Vennila, Zacharias, Wolfgang, Clark, Geoffrey, Siskind, Leah J, Soucy, Patricia, Beverly, Levi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.09.2015; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Bioengineering; Biotechnology; Cancer; Cancer cells; Cancer therapies; Cell adhesion & migration; Cell culture; Cell Culture Techniques - methods; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell survival; Collagen; Cues; Development and progression; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - pathology; Extracellular matrix; Extracellular Matrix - pathology; Fibroblasts; Fibroblasts - pathology; Gene expression; Genetic aspects; Humans; In vitro methods and tests; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - pathology; Medical research; Metastases; Metastasis; Methods; Molecular modelling; Patients; Pharmacology; Physiological aspects; Properties (attributes); Rodents; Substrates; Survival; Three dimensional models; Toxicology; Transformed cells; Tumor cell lines; Tumor cells; Tumor Microenvironment; United States; United States > US; Kentucky
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138065

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.