PMID- 24421272
OWN - NLM
STAT- MEDLINE
DCOM- 20150123
LR  - 20220716
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Print)
IS  - 2045-7634 (Linking)
VI  - 3
IP  - 2
DP  - 2014 Apr
TI  - Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion 
      from TGFbeta1-induced macrophages.
PG  - 201-14
LID - 10.1002/cam4.173 [doi]
AB  - 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 (TGFbeta1) 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, TGFbeta1 induced VEGF 
      production. Basal secretion of VEGF was higher in WT-bone marrow-derived 
      macrophages (BMDM) than in KO-BMDM. TGFbeta1 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 TGFbeta1, increased Arginase I protein levels and galectin-3 
      expression in WT- BMDM, 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 TGFbeta1 signaling pathways.
CI  - (c) 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Machado, Camila Maria Longo
AU  - Machado CM
AD  - Laboratorio de Oncologia Experimental-LIM24, Departamento de Radiologia e 
      Oncologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil; 
      Depto. de Radiologia e Oncologia, Centro de Investigacao Translacional em 
      Oncologia, Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina, 
      Universidade de Sao Paulo, Sao Paulo, Brazil; Laboratorio de Investigacao Medica 
      Radioisotopos-LIM/43, Departamento de Radiologia e Oncologia, Faculdade de 
      Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Andrade, Luciana Nogueira Sousa
AU  - Andrade LN
FAU - Teixeira, Veronica Rodrigues
AU  - Teixeira VR
FAU - Costa, Fabricio Falconi
AU  - Costa FF
FAU - Melo, Camila Morais
AU  - Melo CM
FAU - dos Santos, Sofia Nascimento
AU  - dos Santos SN
FAU - Nonogaki, Suely
AU  - Nonogaki S
FAU - Liu, Fu-Tong
AU  - Liu FT
FAU - Bernardes, Emerson Soares
AU  - Bernardes ES
FAU - Camargo, Anamaria Aranha
AU  - Camargo AA
FAU - Chammas, Roger
AU  - Chammas R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140112
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Galectin 3)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - DNA Methylation
MH  - Galectin 3/genetics/*metabolism
MH  - Humans
MH  - Macrophages/*metabolism
MH  - Male
MH  - Melanoma/*blood supply/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neovascularization, Pathologic/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Transforming Growth Factor beta1/*genetics
MH  - Tumor Microenvironment
MH  - Vascular Endothelial Growth Factor A/biosynthesis/*metabolism
PMC - PMC3987071
OTO - NOTNLM
OT  - Angiogenesis
OT  - galectin-3
OT  - melanoma
OT  - tumor microenvironment
EDAT- 2014/01/15 06:00
MHDA- 2015/01/24 06:00
PMCR- 2014/04/01
CRDT- 2014/01/15 06:00
PHST- 2013/07/30 00:00 [received]
PHST- 2013/11/11 00:00 [revised]
PHST- 2013/11/12 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2015/01/24 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 10.1002/cam4.173 [doi]
PST - ppublish
SO  - Cancer Med. 2014 Apr;3(2):201-14. doi: 10.1002/cam4.173. Epub 2014 Jan 12.