Fibroblast-derived extracellular matrix: an alternative cell culture substrate that alters lung cancer cell line phenotype.

Abstract

Poor lung cancer survival can largely be contributed to the 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 that change the growing tumor’s properties. The Extracellular Matrix (ECM), a main component of the TME, has been shown to change composition during tumor progression, allowing cancer cells to invade tissue and survive 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 understood 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. In our lab, we have adopted a model that examines decellularized human fibroblast-derived ECM as a 3D substrate for growth of lung adenocarcinoma cell lines. It is hypothesized that the interactions between lung cancer cell lines and fibroblast-derived ECM will alter phenotypes important for lung cancer progression. Here, we have characterized the effect of various fibroblast-derived matrices on the properties of various lung cancer adenocarcinoma cell lines. Such altered processes include morphology, growth, and migration. 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.