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Differences in drug transporter expression patterns in human lung cancer cell lines and primary human lung cancer tissues

Drug transporters are a heterogeneous group of transmembrane proteins that build the influx-efflux machinery of every cell. Their role in physiological processes of liver, small intestine, kidneys, and even at the blood brain barrier is very well studied as it presents the basis for the metabolism of the majority of pharmaceutical compounds. Regardless of these facts, the role drug transporters play in normal and diseased lungs remains poor. Over the years lung cancer has proven its position on the top of cancer related deaths being the front runner in incidence, overall mortality as well as in number of new cases. One of the main characteristics of lung cancer contributing to these negative statistics is the relentless multi drug resistance (MDR). To gain a more realistic view of the role drug transporters may have in MDR of lung cancers, primary human lung cancer types, primary human lung tissues not affected by cancer, adenocarcinoma and squamous cell lung carcinoma cell lines, 2 and 3 dimensional co-cultures of primary human healthy cell types (epithelial, endothelial and fibroblast) were studied. 13 drug transporters were selected to be investigated in cancer cell lines representing adeno- and squamous cell carcinomas of the human lung. According to these tests 3 drug transporters with statistically significant differences and one with suggestive values in expression stood out: ABCB1, SLC22A3, SLCO4C1 and ABCG2. Immuno-cytochemical staining showed correlation between mRNA expression levels and positivity of staining in cases of SLC22A3 and SLCO4C1. In case of ABCB1 there was a reverse correlation, which is not the first time to be reported. In case of human tissue samples a stage and score dependent expression patterns were observed as well as differences between tumorous tissue, tumor surrounding non-cancerous tissue and normal lung tissue. Our work suggests evidence that primary human lung tissues express much lower levels of drug transporters than cancerous tissues. We have been able to recognize a stage dependent pattern of drug transporter expression in lung cancers that might help decision-making in therapeutic approaches.

drug transporters; lungcancer; multidrug resistance

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