Stromal Cells Derived from Non-Small Cell Lung Cancer and Normal Lung Tissue Display Mesenchymal Stem Cell Characteristics and Differ in Their Gene Expression Profiles and Functional Behaviour

Stromal microenvironment plays a vital role for the induction and maintenance of solid tumours. However, detailed knowledge on the microenvironment in non-small cell lung cancer (NSCLC) is scanty. Here, we provide a systematic and comparative analysis of genetic and functional properties of autologous stromal cells (SC) derived from NSCLC and microscopically normal lung tissue (NLT) of five newly diagnosed lung cancer patients. SC were derived from 2 large cell, 2 squamous cell, and 1 adenocarcinoma. For all analyses, SC of passage 5 were used. Screening by comparative genetic hybridization revealed no genetic alterations of the SC.

Both, NSCLC-SC and NLT-SC displayed mesenchymal stem cell (MSC) characteristics according to their immunonphenotype and multilineage differentiation potential. However, analysis of growth behaviour and sensitivity to cisplatin revealed significant differences between NSCLC-SC and NLT-SC. NSCLC-SC contained about twice as much colony forming units fibroblast (CFU-f) than NLT-SC and displayed stable colony efficiencies over several passages. This resulted in faster growth kinetics and 27- vs. 12-fold expansion after 10 passages. Moreover, exposure to the cytostatic agent cisplatin demonstrated significantly reduced sensitivity of NSCLC-SC with delayed onset of apoptosis and increased survival of CFU-f. In line with these results, Affymetrix HG U133 Plus 2.0-based arrays and real time PCR showed different expression levels of genes such as ENDOD1, MTP18, QSOX1, or SEMA3C involved in DNA repair, apoptosis, proliferation, and ageing of MSC. Epithelial-to-mesenchymal transition or contamination by tumour cells was excluded by broad surface marker analysis and the absence of epithelium-specific transcripts.

These data strongly suggest the presence of distinct stromal cells in the vicinity of NSCLC that might modulate the cancerogenic process and response to therapy.