SLC31A1/CTR1 - a copper transporter with important implications for platinum-based chemotherapy

Copper is an essential micronutrient that serves as a cofactor in numerous biological processes, but can be toxic when present in excess. Because of this, cells must tightly maintain copper levels. This includes balance between import and export of cellular copper. The major copper importer in humans is the high-affinity copper transporter SLC31A1 or CTR1. The localization of CTR1 varies between cell types, but is commonly found at the plasma membrane and intracellular vesicles [1-3].   

In addition to copper, CTR1 has the ability to transport platinum-containing drugs. One example is a chemotherapeutic drug called cisplatin that is used to treat a variety of cancers. Unfortunately, many types of cancer are resistant to platinum drugs, presenting a major obstacle for achieving maximum drug efficacy. In yeast, western blotting using a CTR1 antibody demonstrated that CTR1 protein levels are negatively regulated by cisplatin treatment [4]. In mice, loss of CTR1 results in decreased platinum accumulation and resulting increased cisplatin resistance [4]. The accumulation of cisplatin in human ovarian cancer cells is limited because of cisplatin-triggered down-regulation and proteasomal degradation of CTR1 [4, 5] . Using CTR1 antibodies, Jandial et al. showed that treatment with a proteasomal inhibitor called bortezomib prevents CTR1 degradation and thus increases platinum uptake in these ovarian cancer cells [5]. Combination therapy with cisplatin and this proteasomal inhibitor thus may be an enhanced treatment strategy.                      

Because abundance of CTR1 may be a biomarker of platinum drug uptake, determining CTR1 levels in a particular cancer type may be an important indicator of future treatment success. Antibodies against CTR1 have been used to determine CTR1 abundance and localization in normal vs. cancerous cells. In these studies, immunohistochemistry can be used to stain tissue arrays using a CTR1 antibody [6] . For example, strong staining was found in certain carcinoid tumors [6] . In another study, CTR1 antibodies were used to examine lung cancer tissue samples from patients who had been treated with platinum-based chemotherapy [7]. Tumor response and tissue platinum concentrations were higher in patients with increased CTR1 levels. Understanding how platinum drugs enter cells and why certain cells are resistant to these drugs is important for developing cancer treatment plants.
Novus Biologiclas offers SLC31A1/CTR1 reagents for your research needs including:

• SLC31A1/CTR1 antibodies
• SLC31A1/CTR1 proteins
• SLC31A1/CTR1 RNAi

PMIDs

1. 12034741
2. 11734551
3. 12023893
4. 12370430
5. 19147760
6. 16709730
7. 24792335

References

1. Eisses, J.F. and J.H. Kaplan, Molecular characterization of hCTR1, the human copper uptake protein. J Biol Chem, 2002. 277(32): p. 29162-71.
2. Lee, J., et al., Biochemical characterization of the human copper transporter Ctr1. J Biol Chem, 2002. 277(6): p. 4380-7.
3. Klomp, A.E., et al., Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1). Biochem J, 2002. 364(Pt 2): p. 497-505.
4. Ishida, S., et al., Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proceedings of the National Academy of Sciences, 2002. 99(22): p. 14298-14302.
5. Jandial, D.D., et al., Enhanced Delivery of Cisplatin to Intraperitoneal Ovarian Carcinomas Mediated by the Effects of Bortezomib on the Human Copper Transporter 1. Clinical Cancer Research, 2009. 15(2): p. 553-560.
6. Holzer, A.K., et al., Expression of the human copper influx transporter 1 in normal and malignant human tissues. J Histochem Cytochem, 2006. 54(9): p. 1041-9.
7. Kim, E.S., et al., Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer. Lung Cancer, 2014. 85(1): p. 88-93.