PMID- 22158049
OWN - NLM
STAT- MEDLINE
DCOM- 20121120
LR  - 20211021
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 31
IP  - 37
DP  - 2012 Sep 13
TI  - Breaking the 'harmony' of TNF-alpha signaling for cancer treatment.
PG  - 4117-27
LID - 10.1038/onc.2011.567 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) binds to two distinct receptors, TNFR1/p55 
      and TNFR2/p75. TNF-alpha is implicated in the processes of tumor growth, survival, 
      differentiation, invasion, metastases, secretion of cytokines and pro-angiogenic 
      factors. We have shown that TNFR2/p75 signaling promotes ischemia-induced 
      angiogenesis via modulation of several angiogenic growth factors. We hypothesized 
      that TNFR2/p75 may promote tumor growth and angiogenesis. Growth of mouse Lewis 
      lung carcinoma (LLC1) and/or mouse melanoma B16 cell was evaluated in wild type 
      (WT), p75 knockout (KO) and double p55KO/p75KO mouse tumor xenograft models. 
      Compared with WT and p55KO/p75KO mice, growth of tumors in p75KO mice was 
      significantly decreased (twofold) in both LLC and B16 tumors. Tumor growth 
      inhibition was correlated with decreases in vascular endothelial growth factor 
      (VEGF) expression and capillary density, as well as bone marrow-derived 
      endothelial progenitor cells incorporation into the functional capillary network, 
      and an increase in apoptotic cells in LLC xenografts. Gene array analysis of 
      tumor tissues showed a decrease in gene expression in pathways that promote tumor 
      angiogenesis and cell survival. Blocking p75 by short-hairpin RNA in cultured 
      LLCs led to increases in TNF-mediated apoptosis, as well as decreases in the 
      constitutive and TNF-mediated expression of angiogenic growth factors (VEGF, HGF, 
      PLGF), and SDF-1alpha receptor CXCR4. In summary, p75 is essential for tumor 
      angiogenesis and survival in highly vascularized murine lung tumor xenografts. 
      Blocking p75 expression may lead to tumor regression. This may represent new and 
      effective therapy against lung neoplasms and potentially tumors of other origin.
FAU - Sasi, S P
AU  - Sasi SP
AD  - Center of Cancer Systems Biology, Brighton, MA 02135, USA.
FAU - Yan, X
AU  - Yan X
FAU - Enderling, H
AU  - Enderling H
FAU - Park, D
AU  - Park D
FAU - Gilbert, H-Y
AU  - Gilbert HY
FAU - Curry, C
AU  - Curry C
FAU - Coleman, C
AU  - Coleman C
FAU - Hlatky, L
AU  - Hlatky L
FAU - Qin, G
AU  - Qin G
FAU - Kishore, R
AU  - Kishore R
FAU - Goukassian, D A
AU  - Goukassian DA
LA  - eng
GR  - R01 HL091983/HL/NHLBI NIH HHS/United States
GR  - R21 AG026777/AG/NIA NIH HHS/United States
GR  - HL091983/HL/NHLBI NIH HHS/United States
GR  - 5R21AG026777-02/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111212
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Pgf protein, mouse)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 144589-93-5 (Placenta Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bone Marrow Cells
MH  - Carcinoma, Lewis Lung/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Chemokine CXCL12/biosynthesis
MH  - Hepatocyte Growth Factor/biosynthesis
MH  - Melanoma, Experimental/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neovascularization, Pathologic/*genetics
MH  - Placenta Growth Factor
MH  - Pregnancy Proteins/biosynthesis
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Receptors, CXCR4/biosynthesis
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/genetics/*metabolism
MH  - Transplantation, Heterologous
MH  - Tumor Microenvironment
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Vascular Endothelial Growth Factors/biosynthesis
MH  - p38 Mitogen-Activated Protein Kinases/biosynthesis/metabolism
PMC - PMC3962797
MID - NIHMS560265
EDAT- 2011/12/14 06:00
MHDA- 2012/12/10 06:00
PMCR- 2014/03/23
CRDT- 2011/12/14 06:00
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2014/03/23 00:00 [pmc-release]
AID - onc2011567 [pii]
AID - 10.1038/onc.2011.567 [doi]
PST - ppublish
SO  - Oncogene. 2012 Sep 13;31(37):4117-27. doi: 10.1038/onc.2011.567. Epub 2011 Dec 
      12.