Alterations in glucose metabolism proteins responsible for the Warburg effect in esophageal squamous cell carcinoma

Autor: Tania Cristina Moita Blanco, Ivanir Martins de Oliveira, Rodolpho Mattos Albano, Luis Felipe Ribeiro Pinto, Ana Rossini, Anke Bergmann, Ester A. Barreto, Luciana Wernersbach Pinto, Paulo Thiago de Souza Santos, Cleber Dario Pinto Kruel
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Adolescent
Esophageal Neoplasms
Cellular differentiation
Pyruvate Kinase
Clinical Biochemistry
Biology
PKM2
Epithelium
Pathology and Forensic Medicine
Malignant transformation
Young Adult
03 medical and health sciences
0302 clinical medicine
Risk Factors
Cell Line
Tumor
Hexokinase
Tumor Microenvironment
medicine
Humans
Glycolysis
RNA
Messenger
Molecular Biology
Aged
Aged
80 and over
Glucose Transporter Type 1
Mucous Membrane
Glucose transporter
Middle Aged
Esophageal cancer
Hypoxia-Inducible Factor 1
alpha Subunit
medicine.disease
Immunohistochemistry
Warburg effect
Gene Expression Regulation
Neoplastic
Glucose
Ki-67 Antigen
030104 developmental biology
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
Female
Esophageal Squamous Cell Carcinoma
Zdroj: Experimental and Molecular Pathology. 101:66-73
ISSN: 0014-4800
Popis: Esophageal squamous cell carcinoma (ESCC) is the most frequent esophageal tumor in the world. ESCC presents late diagnosis, highly aggressive behavior and poor survival. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1 (GLUT-1), and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The objective of this study is to evaluate the alterations of these proteins and their association with clinicopathological data in ESCC. We performed immunohistochemistry to determine HIF-1α, GLUT-1, PKM1, PKM2, HK2 and Ki67-expression in ESCC patients and controls. Also, we used RT-qPCR to evaluated mRNA expression of GLUT-1 in esophageal mucosa of individuals without cancer, but are alcohol drinkers and tobacco smokers. Our results showed the exclusively expression of GLUT-1 in tumors cells and dysplastic samples. We also observed a compartmentalization of the expression of PKM1 and PKM2 in relation to tumor cells and stroma associated to tumor areas. All of the proteins evaluated, excepted GLUT-1, were frequently detected in normal mucosa. No correlations between clinicopathological features and protein expressions were observed. GLUT-1 expression appears in initial tumor lesions and is maintained through ESCC evolution. We reported for the first time PKM1 staining in normal esophagus and ESCC, being mostly present in more differentiated cells.
Databáze: OpenAIRE
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