The reference liver - ABC and SLC drug transporters in healthy donor and metastatic livers

Abstract

Background: Analysis of results and conclusions in studies dedicated to pathology of the liver are usually based on comparison of pathological liver specimens and control/reference (considered as healthy) tissues. There are two main sources of the control liver samples used as the reference livers, i.e. deceased organ donor livers and non-tumorous tissue from metastatic livers, which are also applied for drug transporter investigations. However, no information has yet been published on drug transporters in these two major types of reference livers.

Methods: We explored ABC (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, BSEP) and SLC (NTCP, MCT1, OCT1, OCT3, OAT2, OATP1B1, OATP1B3, OATP2B1) family transporters expression (qPCR) and protein abundance (LC-MS/MS) in healthy donors (n = 9) and metastatic (n = 13) livers.

Results: The analysis of mRNA content revealed significant differences in ABCB11, ABCC1, ABCG2, SLC10A1, SLC16A1, SLCO1B1 and SLCO2B1 gene expression between livers from organ donors and patients who underwent surgical resection of metastatic tumors. The protein abundance of NTCP was significantly higher, whereas of P-gp significantly lower in non-tumorous tissues from metastatic livers. Greater inter-individual variability in protein abundance of all studied transporters in subjects with metastatic colon cancer was also observed.

Conclusions: The results suggest that final conclusions in liver pathology studies may depend on the reference liver tissue used, especially in gene expression studies.

Keywords: Drug transporters; Expression; Liver; Protein abundance.