Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.
Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.
Pinheiro
Céline
C
Life and Health Sciences Research Institute, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
Longatto-Filho
Adhemar
A
Scapulatempo
Cristovam
C
Ferreira
Luísa
L
Martins
Sandra
S
Pellerin
Luc
L
Rodrigues
Mesquita
M
Alves
Venancio A F
VA
Schmitt
Fernando
F
Baltazar
Fátima
F
D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020033:Protein Isoforms; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D020033:Protein Isoforms; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human