title: Modulation of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrin heterodimers during human neuroblastoma cell differentiation.
abstract: Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been analyzed for their capability to adhere to different extracellular matrix (ECM) components. The GI-CA-N cells adhered to all the tested substrates: laminin (LN), type I and type IV collagen (Coll I, Coll IV), vitronectin (VN), and fibronectin (FN). Conversely LAN-5 cells weakly attached to FN and VN, whilst adhesion on LN and Coll I and IV was strong and induced a rapid elongation of cell processes. By means of RT-PCR and immunoprecipitation we showed that the integrin pattern of these two lines was different and could explain their diversity in adhesion capability. Both cell lines express a large amount of the beta 1 integrin subunit, associated with different alpha chains, probably responsible for their adhesion to some ECM proteins. After treatment of LAN-5 cells with biological differentiating agents, such as gamma-interferon, alone or in combination with tumour necrosis factor-alpha (TNF-alpha), or retinoic acid, the levels of alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 integrin expression were enhanced, while the amount of alpha v remained constant. In contrast, treatment of LAN-5 cells with TNF-alpha, that did not induce any maturation, or starvation in 2% foetal calf serum, that inhibited cell proliferation without affecting neural differentiation, did not induce any change in the integrin assessment. Messenger-RNAs for the two alpha 6 isoforms, A and B, were present in both cell lines. However, in LAN-5 cells, the protein product was neither detectable nor inducible by differentiation. Our results confirm the specific modulation of the alpha 1 beta 1 integrin expression in human neuronal development, and show, for the first time, the involvement of alpha 2 beta 1 and alpha 3 beta 1 heterodimers in this maturational process.
authors.affiliation: Oncology Laboratory, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rozzo
authors.forename: P
authors.initials: P
authors.lastname: Ratti
authors.forename: M
authors.initials: M
authors.lastname: Ponzoni
authors.forename: P
authors.initials: P
authors.lastname: Cornaglia-Ferraris
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019096:Vitronectin
chemical_list: D005353:Fibronectins; D006023:Glycoproteins; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019096:Vitronectin; D014212:Tretinoin; D007371:Interferon-gamma; D003094:Collagen