Catalog Number:

GT15068

Product Type:

Affinity Purified

Immunogen Sequence:

Recombinant mouse Endostatin

Host:

Goat

Reactivity:

Mouse

Applications:

ELISA, Western Blot, Immunohistochemistry on frozen sections

Description:

Several lines of direct evidence show that angiogenesis is essential for the growth and persistence of solid tumors and metastases. To stimulate angiogenesis, tumors upregulate a variety of angiogenic factors. Many malignant tumors, however, also generate inhibitors of angiogenesis, including angiostatin. O'Reilly et al. (1994) discovered an angiogenesis inhibitor, designated angiostatin, that specifically inhibits endothelial cell proliferation. They showed that angiostatin is an internal fragment of plasminogen, containing at least 3 of the kringles of plasminogen. Using a rationale similar to that for the isolation of angiostatin, O'Reilly et al. (1997) isolated a 20-kD angiogenesis inhibitor, which they called endostatin, from a murine hemangioendothelioma. They found that endostatin is a C-terminal fragment of collagen XVIII. Systemic therapy with endostatin caused the nearly complete suppression of tumor-induced angiogenesis and strong antitumor activity. Karumanchi et al. (2001) showed that alkaline phosphatase-tagged endostatin bound endothelial cells, revealing 2 binding affinities. Expression cloning identified the cell surface proteoglycan glypican, specifically glypican-1 or glypican-4, as the lower-affinity receptor. Biochemical and genetic studies indicated that the heparan sulfate glycosaminoglycans of glypican were critical for endostatin binding. Furthermore, endostatin selected a specific octasulfated hexasaccharide from a sequence in heparin. Karumanchi et al. (2001) also demonstrated a role for endostatin in renal tubular cell branching morphogenesis and showed that glypicans serve as low-affinity receptors for endostatin in these cells, as in endothelial cells. Antisense experiments suggested the critical importance of glypicans in mediating endostatin activities.

Reference:

O'Reilly, et al.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277-285, 1997

O'Reilly, et al.: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79: 315-328, 1994

Karumanchi, S. A.;et al.: Cell surface glypicans are low-affinity endostatin receptors. Molec. Cell 7: 811-822, 2001

Sertie, A. L.; et al.: Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum. Molec. Genet. 9: 2051-2058, 2000