The online version of this article (https://doi.org/10.1186/s12907-017-0067-7) contains supplementary material, which is available to authorized users.
Endometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development.
MCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.
MCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 (p = 0.003) but not with MCT4 (p = 0.207) expression. High MCT1 expression was associated with reduced overall survival (p = 0.029) and remained statistically significant after adjustment for survival covariates (p = 0.017).
Our data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.
Cancer Research UK Statistics. http://www.cancerresearchuk.org/health-professional/cancer-statistics.
Ma BB, Oza A, Eisenhauer E, Stanimir G, Carey M, Chapman W, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers--a study of the National Cancer Institute of Canada clinical trials group. Int J Gynecol Cancer. 2004;14:650–8. CrossRefPubMed
Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG. Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2010;19:3119–30. CrossRef
Halestrap AP. The SLC16 gene family - structure, role and regulation in health and disease. Mol Asp Med. 2013;34:337–49. CrossRef
de Oliveira AT, Pinheiro C, Longatto-Filho A, Brito MJ, Martinho O, Matos D, et al. Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs). J Bioenerg Biomembr. 2012;44:171–8. CrossRefPubMed
Choi JW, Kim Y, Lee JH, Kim YS. Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder. Urology. 2014;84:245.e249–15. CrossRef
Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO. 2000;19:3896–904. CrossRef
Hashimoto T, Hussien R, Brooks GA. Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex. American J Physiol Endocrinol Metab. 2006;290:E1237–44. CrossRef
- Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer
Amy L. Chadwick
Sarah J. Kitson
Hannah J. Gregson
Vanitha N. Sivalingam
Rhona J. McVey
Stephen A. Roberts
Kay M. Marshall
Kaye J. Williams
Ian J. Stratford
Emma J. Crosbie
- BioMed Central