Nurse cell of Trichinella spp. as a model of long-term cell cycle arrest

Nurse cell (NC), formed from skeletal muscle cells upon infection with parasitic nematode trichina, presents a rare system of long-term suspension in the cell cycle. Signaling pathways and general biological functions of Trichinella spiralis NC, inferred from network analysis of competitive expression microarray data (NC vs. C2C12 myoblasts and myotubes), performed in Ingenuity Pathways Analysis (IPA) software and confirmed by Real-Time PCR, are presented. Assuming 4N DNA content in NC nuclei, its cell cycle arrest is identified herein as a hypermitogenic of G(1)-like type, accompanied by induction of senescence, underpinned by increased expression of p15, p16 and p57 cell cycle inhibitors, as well as overexpression of senescence-associated, beta-galactosidase and numerous secretory factors. Growth factor signaling, with predominant role of EGF, cytokine signaling and G-protein-coupled receptor signaling, are suggested as dominant NC signal transduction pathways. Fos, FosB, STAT6, CREBL2, ID4 and retinoic acid dependent nuclear receptors appear to be the main factors determining NC specific gene transcription. Antigen presentation, complement signaling and beta-amyloid processing pathways are also identified as operating in NC. In general, NC pathology is found to pertain to cancer, as well as other, including immunological and neurological, disorders.