Decellularized lung scaffold-based fibroblasts co-culture method promotes invasion and metastases of human non-small cell lung cancer in vitro

摘要

Tumor invasion and metastases is one of the leading causes of tumor-related death while non-small cell lung cancer(NSCLC)is prone to multiple metastases.T umor microenvironment(TEM),especially extracellular matrix(ECM)and.fibroblasts,plays an important role in tumor metastases and invasion.To better understand the mechanism of NSCLC lung metastases and invasion,we constructed a three-dimensional(3D)co-culture model by seeding A549 tumor cells and human bronchial fibroblasts into decellularized lung scaffolds.Results showed that decellularized mice lung scaffolds retaining intact structure and ECM components,provided a suitable microenvironment for maintaining the viability,morphology of both cells in vitro.3D architecture and pulmonary ECM promoted the mobility/invasion ability of A549 cells by up-regulating the expression of matrix metalloproteinases(MMPs).Meanwhile,factors in TGF-1/Smad4 pathway were significantly up-regulated which may associated with epithelial-mesenchymal transition(EMT)of A549 cells.