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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Angiopoietin-2 promotes disease progression of neuroendocrine tumors

Katharina M Detjen1, Svenja Rieke, Antje Deters

  • 1Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum, Charité-Universitätsmedizin, Berlin, Germany. katharina.detjen@charite.de

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 14, 2010
PubMed
Abstract

Insights

Angiopoietin-2 (Ang-2) is elevated in neuroendocrine tumors and correlates with metastasis and poorer survival. This suggests Ang-2 is a key factor in tumor progression and a potential prognostic marker.

Area of Science:

  • Oncology
  • Vascular Biology
  • Biochemistry

Background:

  • Angiogenesis inhibition is a key therapeutic strategy for neuroendocrine tumors.
  • Angiopoietin-2 (Ang-2) is a critical regulator of tumor angiogenesis.
  • The role of Ang-2 in neuroendocrine tumors requires further investigation.

Purpose of the Study:

  • To investigate the expression and biological significance of Angiopoietin-2 (Ang-2) in human neuroendocrine tumors.
  • To determine if Ang-2 is associated with tumor progression and patient prognosis.

Main Methods:

  • Ang-2 expression was analyzed in tumor specimens and serum using in situ hybridization and ELISA.
  • BON human pancreatic neuroendocrine tumor cells were engineered to overexpress Ang-2.
  • Orthotopic xenografts in nude mice were used to assess tumor growth, metastasis, and microvessel density.

Main Results:

  • Epithelial Ang-2 mRNA expression was specific to neuroendocrine tumors.
  • Ang-2 overexpression in xenografts increased microvessel density and lymphatic metastasis.
  • Circulating Ang-2 levels were elevated in patients and correlated with metastatic disease and shorter survival.

Conclusions:

  • Angiopoietin-2 (Ang-2) induction in neuroendocrine tumors is a clinically relevant mechanism of disease progression.
  • Elevated circulating Ang-2 serves as an adverse prognostic marker in neuroendocrine tumors.

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