Rhabdomyosarcoma and Wilms tumors contain a subpopulation of noggin producing, myogenic cells immunoreactive for lens beaded filament proteins

Abstract

Myo/Nog cells are identified by their expression of the skeletal muscle specific transcription factor MyoD and the bone morphogenetic protein inhibitor noggin, and binding of the G8 monoclonal antibody. Their release of noggin is critical for morphogenesis and skeletal myogenesis. In the adult, Myo/Nog cells are present in normal tissues, wounds and skin tumors. Myo/Nog cells in the lens give rise to myofibroblasts that synthesize skeletal muscle proteins. The purpose of this study was to screen human lens tissue, rhabdomyosarcoma cell lines, and tissue sections from rhabdomyosarcoma, Wilms and tumors lacking features of skeletal muscle for co-localization of antibodies to Myo/Nog cell markers and the lens beaded filament proteins filensin and CP49. Immunofluorescence localization experiments revealed that Myo/Nog cells of the lens bind antibodies to beaded filament proteins. Co-localization of antibodies to G8, noggin, filensin and CP49 was observed in most RC13 and a subpopulation of RD human rhabdomyosarcoma cell lines. Western blotting with beaded filament antibodies revealed bands of similar molecular weights in RC13 and murine lens cells. Human alveolar, embryonal, pleomorphic and spindle cell rhabdomyosarcomas and Wilms tumors contained a subpopulation of cells immunoreactive for G8, noggin, MyoD and beaded filaments. G8 was also co-localized with filensin mRNA. Staining for beaded filament proteins was not detected in G8 positive cells in leiomyosarcomas, squamous and basal cell carcinomas, syringocarciomas and malignant melanomas. Lens beaded filament proteins were thought to be present only in the lens. Myo/Nog-like cells immunoreactive for beaded filaments may be diagnostic of tumors related to the skeletal muscle lineage.

Myo/Nog cells are nonprofessional phagocytes

“…In the failing heart, myofibroblasts were proposed to differentiate from bone marrow-derived cells, pericytes, cells that had undergone an epithelial-mesenchymal transition and resident fibroblasts [ 36 – 38 ]. Myo/Nog cells are present in the embryonic [ 4 ] and adult heart (unpublished data), as well as in tumors [ 9 , 17 ], and therefore, they may contribute to the population of phagocytic myofibroblasts described previously.…”

“…Further evidence of Myo/Nog cells' reactivity to disruptions in homeostasis is their presence in skin tumors and sarcomas [9,17]. In human squamous and basal cell carcinomas and malignant melanomas, the number of Myo/Nog cells correlates with tumor stage and grade [9].…”

Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy

“… 31 – 33 , 38 , 39 , 69 They are the primary, if not exclusive source of noggin in the embryo and adult, including the eyes. 23 , 25 , 31 , 33 , 35 , 37 – 39 , 69 Noggin expression defines the Myo/Nog cells lineage and is not a characteristic of all differentiating myoblasts. 25 Furthermore, Myo/Nog cells do not express cytokeratins in skin tumors and surrounding tissues.…”

Acute Response and Neuroprotective Role of Myo/Nog Cells Assessed in a Rat Model of Focal Brain Injury

“…Myo/Nog cells are normally present in low numbers in all embryonic and adult tissues analyzed thus far (Gerhart et al, 2004(Gerhart et al, , 2006(Gerhart et al, , 2009(Gerhart et al, , 2011(Gerhart et al, , 2012Bravo-Nuevo et al, 2016;Brandli et al, 2017). A variety of stimuli activate, induce proliferation of and recruit Myo/Nog cells, including cell death, epidermal abrasion, tumor formation, surgical wounding of the lens, and retinopathy induced by hypoxia and light damage (Brandli et al, 2017;Gerhart et al, 2014Gerhart et al, , 2019aGerhart et al, , 2020b. In this study, we examined the response of Myo/Nog cells to a focal injury within the brain.…”