Modulation of α1 β1, α2β1, and α3β1 integrin heterodimers during human neuroblastoma cell differentiation

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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 β1 integrin subunit, associated with different α chains, probably responsible for their adhesion to some ECM proteins. After treatment of LAN‐5 cells with biological differentiating agents, such as γ‐interferon, alone or in combination with tumour necrosis factor‐α (TNF‐α), or retinoic acid, the levels of α1β1, α2β1, and α3β1 integrin expression were enhanced, while the amount of α, remained constant. In contrast, treatment of LAN‐5 cells with TNF‐α, 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 α6 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 α1β1 integrin expression in human neuronal development, and show, for the first time, the involvement of α2β1 and α3β1, heterodimers in this maturational process.