GLUT1, MCT1/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma

L.M.C.A. Almeida^1,2,3, R. Silva^4,5, B. Cavadas^1,2, J. Lima^1,2,5, L. Pereira^1,2,5, P. Soares^1,2,5, M. Sobrinho-Simões^1,2,4,5, J.M. Lopes^1,2,4,5 and V. Máximo<sup>1,2,5

1</sup>i3S - Instituto de Investigação e Inovação em Saúde/Institute for Research and Innovation in Health, University of Porto, ²IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, ³ICBAS - Institute of Biomedical Sciences of Abel Salazar, University of Porto, ⁴Department of Pathology, Hospital Centre of S. João and ⁵Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

Offprint requests to: Valdemar Máximo, PhD, IPATIMUP - Instituto de Patologia e Imunologia, Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal. e-mail: vmaximo@ipatimup.pt

Summary. Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10-15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered. The aim of this study was to characterize the metabolic phenotype of pRCCs (subtypes 1-pRCC1 and 2-pRCC2) by evaluating the expression pattern of the glucose transporters (GLUTs) 1 and 4 and the monocarboxylate transporters (MCTs) 1 and 4, as well as their chaperon CD147. We analysed the clinico-pathological data and the protein and mRNA expression of GLUT1, GLUT4 and MCT1, MCT4 and CD147 in tumours from Porto and TCGA series (http://cancergenome.nih.gov/), respectively. With the exception of GLUT4, plasma membrane expression of all proteins was frequently observed in pRCCs. GLUT1 and MCT1 membrane overexpression was significantly higher in pRCC2 and significantly associated with higher pN-stage and higher Fuhrman grade. Overexpression of GLUT1, MCT1/4 and CD147, supports the metabolic reprograming in pRCCs. MCT1 expression was associated with pRCC aggressiveness, regardless of the tumour histotype. Histol Histopathol 32, 1029-1040 (2017)

Key words: Papillary renal cell carcinoma pRCC1, pRCC2, Glucose Transporter, Monocarboxylate transporter

DOI: 10.14670/HH-11-863