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Updated: May 26, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Breaking the 'harmony' of TNF-α signaling for cancer treatment

S P Sasi1, X Yan, H Enderling

  • 1Center of Cancer Systems Biology, Brighton, MA 02135, USA.

Oncogene
|December 14, 2011
PubMed

Insights

Blocking tumor necrosis factor receptor 2 (TNFR2/p75) significantly reduced tumor growth and angiogenesis in mouse models. This suggests targeting TNFR2/p75 could be a novel therapy for lung neoplasms.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor necrosis factor-alpha (TNF-α) interacts with TNFR1/p55 and TNFR2/p75 receptors.
  • TNF-α signaling is involved in tumor growth, survival, invasion, and angiogenesis.
  • Previous studies indicated TNFR2/p75 signaling promotes angiogenesis.

Purpose of the Study:

  • To investigate the role of TNFR2/p75 in promoting tumor growth and angiogenesis.
  • To evaluate the therapeutic potential of targeting TNFR2/p75 in murine lung tumor models.

Main Methods:

  • Tumor xenograft models using Lewis lung carcinoma (LLC1) and melanoma B16 cells in wild type, p75 knockout, and double knockout mice.
  • Analysis of tumor growth, vascularization (VEGF, capillary density, endothelial progenitor cells), apoptosis, and gene expression.
  • In vitro studies using short-hairpin RNA to block p75 in LLC cells.

Main Results:

  • Tumor growth was significantly reduced (twofold) in p75 knockout mice compared to controls.
  • Reduced tumor growth correlated with decreased VEGF expression, capillary density, and endothelial progenitor cell incorporation.
  • Blocking p75 in vitro increased TNF-mediated apoptosis and decreased expression of angiogenic factors and CXCR4.

Conclusions:

  • TNFR2/p75 signaling is essential for tumor angiogenesis and survival in highly vascularized lung tumors.
  • Blocking p75 expression can inhibit tumor growth and may lead to tumor regression.
  • Targeting TNFR2/p75 represents a potential new therapeutic strategy for lung neoplasms and other cancers.

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