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Related Experiment Videos

Organogenesis and angiogenin

B L Vallee1, J F Riordan

  • 1Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

Cellular and Molecular Life Sciences : CMLS
|December 31, 1997
PubMed
Summary

Researchers identified angiogenin, a potent blood vessel formation stimulator, and found that inhibiting it blocks tumor growth. This discovery offers a promising therapeutic strategy for treating malignant diseases.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for tumor growth.
  • Human colon adenocarcinoma cells (HT-29) conditioned medium was screened for angiogenesis-inducing factors.
  • The 'organizer' hypothesis inspired the search for these factors.

Purpose of the Study:

  • To isolate and characterize an angiogenesis-inducing factor from HT-29 cell conditioned medium.
  • To investigate the properties, structure-function relationship, and therapeutic potential of the isolated factor, named angiogenin.
  • To explore angiogenin inhibition as a strategy for cancer treatment.

Main Methods:

  • Isolation of angiogenin from conditioned medium.
  • Biochemical and structural analysis of angiogenin, comparing it to ribonuclease A (RNase A).
  • In vitro and in vivo studies using angiogenin inhibitors (monoclonal antibody, actin) to assess their effect on angiogenesis and tumor growth.

Main Results:

  • Angiogenin, a 14 kD protein homologous to RNase A, was isolated as a potent angiogenesis stimulator.
  • Angiogenin exhibits low enzymatic activity but possesses a critical cell binding site essential for angiogenesis.
  • Inhibitors of angiogenin, including a monoclonal antibody and actin, effectively blocked angiogenesis in vitro and suppressed tumor growth in vivo.
  • Tumor growth inhibition was observed in HT-29 xenografts and tumors derived from other human cell lines.

Conclusions:

  • Angiogenin is a key mediator of angiogenesis with therapeutic potential for cancer treatment.
  • Inhibition of angiogenin's activity presents a viable strategy for combating malignant diseases.
  • Non-cytotoxic inhibitors like actin demonstrate significant anti-tumor effects without observable toxicity.

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