ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain.
OBJECTIVE
To study the expression and function of the brain-specific proteinase deficient disintegrins, ADAM11 and ADAM22 (a disintegrin and metalloproteinase).


METHODS
Specimens of low- and high-grade gliomas and normal brain were analyzed for ADAM11 and ADAM22 expression using Western blotting. The effects of overexpression of ADAM11 and ADAM22 in glioma cells on growth were analyzed using bromodeoxyuridine incorporation linked to immunocytochemistry. Similarly analyzed were the effects on cell proliferation of bacterially expressed glutathione S-transferase fusion proteins with the disintegrin domain of ADAM11 and ADAM22.


RESULTS
ADAM22 is expressed in normal brain and some low-grade gliomas, but not in high-grade gliomas, whereas ADAM11 is expressed in all low- and high-grade gliomas. In vitro, ADAM22 inhibits cellular proliferation of glioma derived astrocytes. The growth inhibition appears to be mediated by interactions between the disintegrin domain of ADAM22 and specific integrins expressed on the cell surface. This growth inhibition can be avoided by over-expression of integrin linked kinase.


CONCLUSIONS
ADAM22, a brain-specific cell surface protein, mediates growth inhibition using an integrin dependent pathway. It is expressed in normal brain but not in high-grade gliomas. A related protein, ADAM11, has only a minor effect on cell growth, and its expression is unchanged in low- and high-grade gliomas.
D'Abaco
Giovanna M
GM
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia.
Ng
Ken
K
Paradiso
Lucy
L
Godde
Nathan J
NJ
Kaye
Andrew
A
Novak
Ulrike
U
D051722:ADAM Proteins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019483:Disintegrins / Q000235:genetics / Q000502:physiology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012016:Reference Values; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000099200:Scaffold Protein ILK
D051722:ADAM Proteins; D019483:Disintegrins; D005982:Glutathione Transferase; D039302:Integrin alphaVbeta3; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK; C090222:ADAM11 protein, human; C498474:ADAM22 protein, human