Mesenchymal Stromal Cells Derived from Human Non-Small Cell Lung Cancer, Normal Lung Tissue, and Bone Marrow: Differences in Frequency, Cytogenetics, Proliferation Behavior, and Chemosensitivity - Implications for Cancer Therapy.

Abstract Stromal microenvironment plays a vital role for the induction and maintenance of solid tumors. Knowledge on the nature and impact of the tumor-microenvironment in lung cancer is still inadequate. In this study, we investigated and compared stromal cells (SC) derived from non-small cell lung cancer (NSCLC), normal lung tissue (NLT), and bone marrow (BM) for the presence and properties of mesenchymal stromal cells (MSC). NSCLC-SC and NLT-SC displayed mesenchymal morphology, immunophenotype, and differentiation capabilities implying their MSC character. However, their frequency, proliferation behavior, and chemosensitivity varied significantly from BM-MSC and among each other. Colony forming units-fibroblast (CFU-f) were 300-fold less frequent in bone marrow but exhibited an up to 44-fold higher colony efficiency (CE) than in lung. Compared to NLT, NSCLC specimens were four times enriched in CFU-f possessing an unfailing CE over several passages. According to colony size, the proliferation potential of NSCLC-CFU-f was double that of NLT-CFU-f and did not vary with cell density thus indicating an autonomous growth and lack of feedback regulation. Moreover, NSCLC-SC exhibited a markedly reduced sensitivity to cisplatin with delayed apoptosis and faster recovery from cytotoxic damage. In line with functional alterations multicolor-fluorescence in situ hybridization revealed genetic aberrations and chromosomal instability of NSCLC-SC but not of NLT-SC. These data provide evidence for the presence of tumor-specific MSC in NSCLC and suggest the survival of a particular tumor-stroma after chemotherapeutic treatment.