TY - JOUR
T1 - Lactate transporters and vascular factors in HPV-induced squamous cell carcinoma of the uterine cervix
AU - Pinheiro, Céline
AU - Garcia, Eduardo A.
AU - Morais-Santos, Filipa
AU - Scapulatempo-Neto, Cristovam
AU - Mafra, Allini
AU - Steenbergen, Renske D.M.
AU - Boccardo, Enrique
AU - Villa, Luisa L.
AU - Baltazar, Fátima
AU - Longatto-Filho, Adhemar
N1 - Publisher Copyright:
© 2014 Pinheiro et al.; licensee BioMed Central Ltd.
PY - 2014/10/8
Y1 - 2014/10/8
N2 - Background: Tumour microenvironment is a fundamental aspect of tumour behaviour, modulating important events as cancer cell migration and invasion, as well as angiogenesis and metastisation. Among other microenvironment features, hypoxia and acidity play important roles in this modulation. As the metabolic reprogramming of cancer cells induces extracellular acidity, which in turn induces angiogenesis, and hypoxia induces both the metabolic reprogramming and angiogenesis, the present study aims to evaluate the immunohistochemical expression of a variety of metabolic and vascular markers as common targets of the hypoxic microenvironment in a series of cervical squamous cells carcinoma, as well as using an in vitro 3D culture model.Methods: Immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX was assessed in a series of 28 chronic cervicitis, 34 LSIL, 29 HSIL, 38 cases of squamous cells carcinoma (SCC), as well as in in vitro 3D culture of keratinocytes expressing HPV genes. Furthermore, VEGF family members' expression was assessed in the SCC cases. The expression profiles were associated with patients' clinicopathological parameters.Results: We found an increase of MCT4 expression along progression to malignancy in cervical samples. Also, MCT4 was associated with CD147 and CAIX expression. VEGF-A expression was more frequently found in cases without MCT1 expression. Both MCT4 and CD147 were more frequently expressed in younger patients at diagnosis while no associations were found between VEGF family and clinicopathological parameters. Finally, we show evidence for the upregulation of MCT4, as well as CD147 and CAIX, after HPV transfection.Conclusions: The results herein presented point at MCT4 as a promising therapeutic target in squamous cells carcinoma of the uterine cervix. Importantly, we show a possible association between lactate transport and angiogenesis, which should be further explored.
AB - Background: Tumour microenvironment is a fundamental aspect of tumour behaviour, modulating important events as cancer cell migration and invasion, as well as angiogenesis and metastisation. Among other microenvironment features, hypoxia and acidity play important roles in this modulation. As the metabolic reprogramming of cancer cells induces extracellular acidity, which in turn induces angiogenesis, and hypoxia induces both the metabolic reprogramming and angiogenesis, the present study aims to evaluate the immunohistochemical expression of a variety of metabolic and vascular markers as common targets of the hypoxic microenvironment in a series of cervical squamous cells carcinoma, as well as using an in vitro 3D culture model.Methods: Immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX was assessed in a series of 28 chronic cervicitis, 34 LSIL, 29 HSIL, 38 cases of squamous cells carcinoma (SCC), as well as in in vitro 3D culture of keratinocytes expressing HPV genes. Furthermore, VEGF family members' expression was assessed in the SCC cases. The expression profiles were associated with patients' clinicopathological parameters.Results: We found an increase of MCT4 expression along progression to malignancy in cervical samples. Also, MCT4 was associated with CD147 and CAIX expression. VEGF-A expression was more frequently found in cases without MCT1 expression. Both MCT4 and CD147 were more frequently expressed in younger patients at diagnosis while no associations were found between VEGF family and clinicopathological parameters. Finally, we show evidence for the upregulation of MCT4, as well as CD147 and CAIX, after HPV transfection.Conclusions: The results herein presented point at MCT4 as a promising therapeutic target in squamous cells carcinoma of the uterine cervix. Importantly, we show a possible association between lactate transport and angiogenesis, which should be further explored.
KW - Angiogenesis
KW - Cervical carcinoma
KW - Hypoxia
KW - Lymphangiogenesis
KW - Metabolic reprogramming
KW - Monocarboxylate transporter
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84908068548&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-14-751
DO - 10.1186/1471-2407-14-751
M3 - Article
C2 - 25296855
AN - SCOPUS:84908068548
SN - 1471-2407
VL - 14
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 751
ER -