The Individuality of Tumour-Stroma Interaction in Non-Small Cell Lung Cancer: Insights from Funtional and Molecular Analysis

Tumour-stroma interaction plays a significant role for malignant growth. Here, we analyzed the functional and molecular sequels of interaction in a non-contact co-culture model consisting of the lung adenocarcinoma cell lines A549, H23, or H1703 and primary stromal cells (SC) derived from normal lung tissue (NLT) and non-small cell lung cancer (NSCLC) lesions of newly diagnosed NSCLC patients. The behavioural alterations of the tumour cells upon exposure to SC are shown below:

	Proliferation and colony efficiency		Migration		Adhesion		Invasion		Chemosensitivity (cisplatin)
	NSCLC-SC	NLT-SC	NSCLC-SC	NLT-SC	NSCLC-SC	NLT-SC	NSCLC-SC	NLT-SC	NSCLC-SC	NLT-SC
A549	↑	↓	↑	↗	↔	↔	↑	↗	↓	↓
H23	↔	↓	↔	↔	↑	↑	↔	↔	↑	↑
H1703	↑	↓	↑	↗	↔	↔	↑	↗	↓	↓

In summary, these data demonstrate: (1) that tumour cells – although derived from the same histology – responded differently to SC, (2) that the origin of SC played a role for the impact on proliferation and colony efficiency, but not for functions associated with metastasis, and (3) that migration and invasion were affected in a similar direction confirming a coupled process. Moreover, detailed analysis of chemosensitivity revealed that SC altered the mode of cytotoxic action: In mono-cultures, cisplatin induced apoptosis of A549 and necrosis of H23 and H1703 cells whereas exposure to SC induced apoptosis of all three cell lines. In line with these results expression profiling of tumour cells before and after 48 hours exposure to SC by Affymetrix HG U133 Plus 2.0-based arrays and real time PCR demonstrated cell line specific expression patterns and individual alterations upon exposure to SC. Differences between NLT-SC- and NSCLC-SC-induced changes were also present but less distinctive.

These data show an individual pattern of tumour-stroma interaction that is determined by both, the properties of the tumour cells and the characteristics of the stromal environment.