CD44 variant isoforms associate with tetraspanins and EpCAM.
The metastasizing subline of the rat pancreatic adenocarcinoma BSp73 expresses a set of membrane molecules, the combination of which has not been detected on non-metastasizing tumor lines. Hence, it became of interest whether these molecules function independently or may associate and exert specialized functions as membrane complexes. Separation of CD44v4-v7 containing membrane complexes in mild detergent revealed an association with the alpha3 integrin, annexin I, EpCAM, and the tetraspanins D6.1A and CD9. EpCAM and the tetraspanins associate selectively with CD44 variant (CD44v), but not with the CD44 standard (CD44s) isoform. The complexes are found in glycolipid-enriched membrane (GEM) microdomains, which are dissolved by stringent detergents, but the complexes are not destroyed by methyl-beta-cyclodextrin (MbetaCD) treatment, which implies that complex formation does not depend on a lipid-rich microenvironment. However, a complex-associated impact on cell-matrix and cell-cell adhesion as well as on resistance towards apoptosis essentially depended on the location in GEMs. Thus, CD44v-specific functions may well be brought about by complex formation of CD44v with EpCAM, the tetraspanins, and the alpha3 integrin. Because CD44v4-v7-EpCAM complex-specific functions strictly depended on the GEM localization, linker or signal-transducing molecules associating with the complex are likely located in GEMs.
Schmidt
Dirk-Steffen
DS
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.
Klingbeil
Pamela
P
Schnölzer
Martina
M
Zöller
Margot
M
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003505:Cyclodextrins / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D000071858:Epithelial Cell Adhesion Molecule; D014644:Genetic Variation; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010190:Pancreatic Neoplasms / Q000473:pathology; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D047392:beta-Cyclodextrins
D017305:Annexin A1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D003505:Cyclodextrins; D003902:Detergents; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors; D016023:Integrins; D008565:Membrane Proteins; D020033:Protein Isoforms; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin