Tumstatin, the NC1 domain of {alpha}3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth

Journal Article · Fri Jul 29 04:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.05.130· OSTI ID:20710868

Hamano, Yuki ^[1]; Kalluri, Raghu ^[1]

---

1. Center for Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215 (United States)

Angiogenesis, the formation of new blood vessels, is required for physiological development of vertebrates and repair of damaged tissue, but in the pathological setting contributes to progression of cancer. During tumor growth, angiogenesis is supported by up-regulation of angiogenic stimulators (pro-angiogenic) and down-regulation of angiogenic inhibitors (anti-angiogenic). The switch to the angiogenic phenotype (angiogenic switch) allows the tumors to grow and facilitate metastasis. The bioactive NC1 domain of type IV collagen {alpha}3 chain, called tumstatin, imparts anti-tumor activity by inducing apoptosis of proliferating endothelial cells. Tumstatin binds to {alpha}V{beta}3 integrin via a mechanism independent of the RGD-sequence recognition and inhibits cap-dependent protein synthesis in the proliferating endothelial cells. The physiological level of tumstatin is controlled by matrix metalloproteinase-9, which most effectively cleaves it from the basement membrane and its physiological concentration in the circulation keeps pathological angiogenesis and tumor growth in check. These findings suggest that tumstatin functions as an endogenous inhibitor of pathological angiogenesis and functions as a novel suppressor of proliferating endothelial cells and growth of tumors.

• OSTI ID: 20710868
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 333; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BIOLOGICAL REPAIR
BLOOD VESSELS
CELL PROLIFERATION
COLLAGEN
GENE REGULATION
METASTASES
NEOPLASMS
PHENOTYPE
SWITCHES
SYNTHESIS
VERTEBRATES