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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

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Published on: November 23, 2014

Kringle structures and antiangiogenesis

Yihai Cao1, Renhai Cao, Niina Veitonmäki

  • 1Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden. yihai.cao@mtc.ki.se

Current Medicinal Chemistry. Anti-Cancer Agents
|April 8, 2003
PubMed

Insights

Kringle domains, found in proteins like angiostatin, are crucial for inhibiting tumor angiogenesis. Proteolytic processing reveals these cryptic fragments, offering a new strategy for developing anti-cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The adult vascular system maintains quiescence through a balance of pro-angiogenic and anti-angiogenic factors.
  • Tumors disrupt this balance, producing specific inhibitors like angiostatin to promote their growth.
  • Angiostatin, a tumor-derived angiogenesis inhibitor, is under investigation for cancer therapy due to its potent anti-tumor effects.

Purpose of the Study:

  • To review the structural and functional relationships of kringle domains in regulating angiogenesis and tumor growth.
  • To explore the potential of kringle domains as a basis for identifying novel angiogenesis inhibitors.
  • To highlight the role of proteolytic processing in uncovering anti-angiogenic activity.

Main Methods:

  • Review of existing literature on angiostatin, kringle domains, and angiogenesis.
  • Analysis of structural features of kringle domains and their correlation with anti-angiogenic activity.
  • Examination of the mechanism of proteolytic processing in releasing active kringle fragments.

Main Results:

  • Angiostatin, composed of kringle domains from plasminogen, effectively inhibits tumor angiogenesis and growth.
  • Disulfide bond-linked kringle architectures are essential for angiostatin's anti-angiogenic activity.
  • Kringle fragments from various proteins also exhibit anti-angiogenic properties, often requiring cleavage from parental proteins.

Conclusions:

  • Kringle domains represent a conserved structural motif with specific anti-angiogenic activity.
  • Proteolytic processing is critical for revealing the anti-angiogenic potential of these "cryptic" kringle fragments.
  • Kringle domains offer a promising structural framework for the development of new anti-cancer therapeutics targeting angiogenesis.

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