Abstract PS18-48: Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue

Abstract

Abstract Essential nutrient uptake required for cell growth and survival is mediated by Solute Carrier (SLC) transporters both physiologically and in cancers. The SLC super-family encompasses sub-families of transport proteins including organic anion transporters (OAT), organic cation transporters (OCT) and organic anion transporting polypeptides (OATP). SLCs transport a vast array of endogenous and exogenous substances, including estrogen, its conjugates, and clinically relevant anti-cancer drugs. Accumulating evidence suggests that SLC transporters are differentially expressed in hormone-responsive and hormone non-responsive breast cancers, which could influence breast cancer pathogenesis, both in disease progression and treatment resistance. We investigated whether SLC transporters are differentially expressed in different breast cancer cell lines and in human breast cancer tissue. First, bulk cells from the breast cancer cell lines MCF-7 (hormone responsive) and MDA-MB-231 (hormone non-responsive) were analysed for differential expression of SLCs using sq-PCR and RT-PCR. 8 of 11 SLCO and 10 of 14 SLC22 transporters were expressed in at least one cell line. Transporter expression was either similar or lower in MCF-7 cells compared to MDA-MB-231 cells, with the exception of SLCO2A1, SLCO4C1, SLCO5A1 and SLC22A5 which were higher in MCF-7 cells. mRNA expression of SLCs was then compared between both cell lines and human breast cancer tissue. The latter showed an expression pattern largely reminiscent of the MCF-7 cells. Because these techniques measure the average level of expression shown by a pooled cell population, there is the potential disadvantage that cell heterogeneity is masked. To help address this, Single Cell RNA Sequencing (scRNA-Seq) was performed using the 10x Genomics Chromium Single Cell 3’ platform and NovaSeq Technologies to compare SLC transporter expression between the cell lines. Together these results provide evidence for differences in SLC transporter expression between cell lines and cancer tissues that may contribute to cancer progression. Citation Format: Rachel Jane Sutherland, Annette Meeson, Simon Lowes. Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-48.