Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.2.1.166 extracted from

  • Gutter-Kapon, L.; Alishekevitz, D.; Shaked, Y.; Li, J.P.; Aronheim, A.; Ilan, N.; Vlodavsky, I.
    Heparanase is required for activation and function of macrophages (2016), Proc. Natl. Acad. Sci. USA, 113, E7808-E7817 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.2.1.166

Application

Application Comment Organism
drug development the emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs for humans Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of heparanase-knockout (Hpa-KO) mice, reduced cytokine expression and motility of heparanase-deficient macrophages, phenotype, overview Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
heparan sulfate + H2O Mus musculus
-
 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q6YGZ1
-
-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell
-
 Mus musculus
-
Lewis lung carcinoma cell
-
 Mus musculus
-
macrophage
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
heparan sulfate + H2O
-
 Mus musculus ?
-
 ?

Synonyms

Synonyms Comment Organism
endo-beta-glucuronidase
-
 Mus musculus
HPA
-
 Mus musculus

General Information

General Information Comment Organism
malfunction macrophages from heparanase-knockout (Hpa-KO) mice express lower levels of cytokines (e.g. TNFalpha, interleukin 1-beta) and exhibit lower motility and phagocytic capacities. Inoculation of control monocytes togetherwith Lewis lung carcinoma (LLC) cells into Hpa-KO mice results in nearly complete inhibition of tumor growth. In striking contrast, inoculating LLC cells together with monocytes isolated from Hpa-KO mice does not affect tumor growth, indicating that heparanase is critically required for activation and function of macrophages Mus musculus
physiological function heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate (HS) side chains presumably at sites of low sulfation. Heparanase is critically required for activation and function of macrophages. Heparanase activates Erk, p38, and JNK signaling in macrophages by a linear cascade, leading to increased c-Fos levels and induction of cytokine expression in a manner that apparently does not require heparanase enzymatic activity. Heparanase is a key mediator of macrophage activation and function in tumorigenesis and cross-talk with the tumor microenvironment. Heparanase from the tumor microenvironment supports tumor growth. Mutant Hpa-KO macrophages do not attenuate tumor growth Mus musculus