PMID- 21159663
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20201222
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 3
DP  - 2011 Feb 1
TI  - Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in 
      melanoma enhances tumor infiltration and immunosuppression.
PG  - 812-21
LID - 10.1158/0008-5472.CAN-10-2698 [doi]
AB  - Melanoma progression is associated with the expression of different growth 
      factors, cytokines, and chemokines. Because TGFbeta1 is a pleiotropic cytokine 
      involved not only in physiologic processes but also in cancer development, we 
      analyzed in A375 human melanoma cells, the effect of TGFbeta1 on monocyte 
      chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two 
      known factors responsible for melanoma progression. TGFbeta1 increased the 
      expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk 
      between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen 
      activated protein kinase) signaling pathways. Supernatants from TGFbeta1-treated 
      A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, 
      expressed high levels of TGF,beta1, bFGF, and VEGF mRNA. Moreover, these 
      supernatants also inhibited functional properties of dendritic cells through 
      IL-10-dependent mechanisms. When using in vitro, the TGFbeta1-blocking peptide P144, 
      TGFbeta1-dependent Smad3 phosphorylation, and expression of MCP-1 and IL-10 were 
      inhibited. In vivo, treatment of A375 tumor-bearing athymic mice with P144 
      significantly reduced tumor growth, associated with a lower macrophage infiltrate 
      and decreased intratumor MCP-1 and VEGF levels, as well as angiogenesis. Finally, 
      in C57BL/6 mice with B16-OVA melanoma tumors, when administered with 
      immunotherapy, P144 decreased tumor growth and intratumor IL-10 levels, linked to 
      enhanced activation of dendritic cells and natural killer cells, as well as 
      anti-OVA T-cell responses. These results show new effects of TGFbeta1 on melanoma 
      cells, which promote tumor progression and immunosuppression, strongly 
      reinforcing the relevance of this cytokine as a molecular target in melanoma.
FAU - Diaz-Valdes, Nancy
AU  - Diaz-Valdes N
AD  - Universidad de Navarra, Centro de Investigacion Medica Aplicada, Area de 
      Hepatologia y Terapia Genica, Pamplona, Spain.
FAU - Basagoiti, Maria
AU  - Basagoiti M
FAU - Dotor, Javier
AU  - Dotor J
FAU - Aranda, Fernando
AU  - Aranda F
FAU - Monreal, Inaki
AU  - Monreal I
FAU - Riezu-Boj, Jose Ignacio
AU  - Riezu-Boj JI
FAU - Borras-Cuesta, Francisco
AU  - Borras-Cuesta F
FAU - Sarobe, Pablo
AU  - Sarobe P
FAU - Feijoo, Esperanza
AU  - Feijoo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101215
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chemokine CCL2/*biosynthesis
MH  - Female
MH  - Humans
MH  - Interleukin-10/*biosynthesis/immunology
MH  - MAP Kinase Signaling System
MH  - Melanoma/*immunology
MH  - Melanoma, Experimental/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - Monocytes/drug effects/immunology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Smad3 Protein/metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
EDAT- 2010/12/17 06:00
MHDA- 2011/05/03 06:00
CRDT- 2010/12/17 06:00
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
AID - 0008-5472.CAN-10-2698 [pii]
AID - 10.1158/0008-5472.CAN-10-2698 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Feb 1;71(3):812-21. doi: 10.1158/0008-5472.CAN-10-2698. Epub 
      2010 Dec 15.