Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGF beta 1-induced macrophages

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Arquivos
art_MACHADO_Galectin3_disruption_impaired_tumoral_angiogenesis_by_reducing_VEGF_2014.PDF (1.66 MB)
Citações na Scopus
41
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
TEIXEIRA, Veronica Rodrigues
COSTA, Fabricio Falconi
NONOGAKI, Suely
LIU, Fu-Tong
CAMARGO, Anamaria Aranha
Citação
CANCER MEDICINE, v.3, n.2, p.201-214, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
In order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGF beta 1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68(+) -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68(+) cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGF beta 1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGF beta 1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGF beta 1, increased Arginase I protein levels and galectin-3 expression in WTBMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGF beta 1 signaling pathways.
Palavras-chave
Angiogenesis, galectin-3, melanoma, tumor microenvironment
URI
https://observatorio.fm.usp.br/handle/OPI/9328
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - LIM/43
Artigos e Materiais de Revistas Científicas - ODS/03