Biological Characteristics of Stromal Cells Differ Between Primary Lung Adenocarcinoma, Peritumoral Lung, and Distal Lung Tissues.

BACKGROUND: Stromal cells are known to play critical roles in the development and progression of solid tumors including lung cancers. This study was proposed to clarify the biological features of stromal cells from intratumoral, peritumoral lung, and distal lung tissues of primary lung adenocarcinoma patients. METHODS: Surgically resected lung lobes containing primary adenocarcinoma were used for isolating stromal cells. Tumor tissue, peritumoral lung tissue, and distal lung tissue were sampled and cut into small pieces for culture as "explants." The biological features of stromal cells were evaluated by cell isolating efficiency, cell morphology, cell surface marker, gene expression profile, and cytokine secretion. RESULTS: Spindle shaped fibroblast-like cells were outgrown successfully from the "explants" with comparable efficiency among different tissues. All outgrowth cells were vimentin-positive and cytokeratin-negative, consistent with stromal cell phenotypes. Quantitative analysis on the width-to-length ratio of cells indicated different morphological differences among stromal cells. Moreover, the expression of α-smooth muscle actin (α-SMA), a marker for cancer-associated fibroblasts (CAFs), was more extensively observed in stromal cells from tumor tissues than others and, its PCR array showed higher expression of extracellular matrix (ECM)-related factors COL11A1 and TIMP3, in contrast, cytokine array analysis revealed more abundant release of immune-suppressive factors from stromal cells of peritumoral tissues. CONCLUSION: Stromal cells from tumor, peritumoral, and distal lung tissues display distinct biological characteristics. Further investigation is needed to elucidate their specific roles in tumor progression.