title: Release of cell surface proteoglycans from differentiating colon cells proceeds by cleavage of lipophilic anchor peptides.
abstract: Heparan sulphate proteoglycans are rapidly released from VACO 10MS colon cancer cells that are triggered with phorbol esters to undergo terminal differentiation. This lag-free temperature-sensitive process is correlated with a conversion of the lipophilic proteoglycans of the cell surface into non-lipophilic proteoglycans that accumulate in the culture medium. The released proteoglycans are very similar to their lipophilic precursors in size, buoyant density and glycosaminoglycan characteristics; however, they exhibit slightly smaller core proteins after chemical and enzymic deglycosylation. The lipophilicity of the larger-sized core proteins of the cell-associated proteoglycans is also correlated with the presence of an easily iodinatable domain; this domain is missing in the released proteoglycans. Exogenous proteases (i.e. chymotrypsin, V8, trypsin and proteinase K) readily cleave this segment from the larger protease-resistant region of the proteoglycan structure. It is also released intact by treatment of the isolated proteoglycans with methanolic HCl. This component appears to be peptide in character, in that proteases readily degrade it and release iodotyrosines when the precursor has been iodinated. No evidence for the presence of covalently attached fatty acids in the cell-associated proteoglycans was found. These results are consistent with the hypothesis that the altered proteoglycan metabolism that is associated with the phorbol-ester-induced terminal differentiation of certain human colon cancer cells ensues upon the activation of a membrane-localized protease that cleaves a lipophilic anchor segment from the cell surface proteoglycans.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
authors.forename: J A
authors.initials: JA
authors.lastname: McBain
authors.forename: G C
authors.initials: GC
authors.lastname: Mueller
mesh_terms: D002454:Cell Differentiation; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D011493:Protein Kinase C / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism*; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000378:metabolism
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008565:Membrane Proteins; D011493:Protein Kinase C; D011509:Proteoglycans; D013755:Tetradecanoylphorbol Acetate; D014758:Viral Core Proteins