Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

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Pinheiro, Celine ^{[1, 2, 3, 4]} ; Garcia, Eduardo A. ^{[2, 3]} ; Morais-Santos, Filipa ^{[1, 4]} ; Moreira, Marise A. R. ^[5] ; Almeida, Fabio M. ^[5] ; Jube, Luiz F. ^[6] ; Queiroz, Geraldo S. ^[6] ; Paula, Elbio C. ^[6] ; Andreoli, Maria A. ^{[7, 8]} ; Villa, Luisa L. ^{[7, 8, 9]} ; Longatto-Filho, Adhemar ^{[1, 7, 10, 4]} ; Baltazar, Fatima ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[2] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil

^[3] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Sao Paulo - Brazil

^[4] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, P-4710057 Braga - Portugal

^[5] Univ Fed Goias, Sch Med, Dept Pathol, Goiania, Go - Brazil

^[6] Hosp Araujo Jorge, Goiania, Go - Brazil

^[7] Inst Nacl Ciencia & Tecnol HPV INCT HPV, Sao Paulo - Brazil

^[8] Santa Casa Sao Paulo Med Sch, Sao Paulo - Brazil

^[9] Univ Sao Paulo, Fac Med, Sao Paulo State Canc Inst, Dept Radiol, Ctr Translat Oncol Invest, Sao Paulo - Brazil

^[10] Univ Sao Paulo, Sch Med, Lab Med Invest LIM 14, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC CANCER; v. 15, NOV 2 2015.
• Citações Web of Science: 9

Resumo

Background: Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells. This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux, besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy, by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological behavior. Methods: The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles were associated with patients' clinicopathological parameters. Results: Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis. Conclusions: The results herein presented provide additional evidence for a crosstalk between deregulating cellular energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer progression and aggressiveness in adenocarcinomas. (AU)

• Processo FAPESP: 08/03232-1 - HPV e microambiente tumoral
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático