Summary
Myosin isoform expression was analyzed in experimental rhabdomyosarcoma (RMS) using monoclonal antibodies (mAbs) and immunofluorescence techniques. Tumors induced by inoculating newborn rats with Moloney murine sarcoma virus (Mo-MSV) were examined 30–90 days after birth. Nine tumors and two lymph node metastases were studied by direct, indirect, and double immunofluorescence assays using a panel of five anti-myosin mAbs. The mAb BF-45 was specifically reactive with embryonic myosin heavy chain (MHC), mAb BF-34 was specific for a neonatal MHC epitope, mAb BF-B6 was directed against an epitope present in both embryonic and neonatal MHC, and mAbs BF-F3 and BF-32 detected epitopes present in adult MHC isoforms. Anti-desmin antibodies were also used for comparison. The results of this study show that: (1) the majority of neoplastic cells stained for desmin while only a minority of neoplastic cells were labeled by anti-myosin antibodies; (2) myosin positive tumor cells contained predominantly embryonic and neonatal MHC types but rare RMS cells reacted exclusively with anti-adult myosin antibodies; and (3) adult and embryonic MHC phenotypes were occasionally detected within the same tumor cell especially in RMS with the longest latencies. Together these results would suggest that the mechanism(s) regulating MHC gene expression in skeletal muscle cells can be altered by the transforming activity of Mo-MSV.
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References
Altmannsberger M, Weber K, Droste R, Osborn M (1982) Desmin is a specific marker for rhabdomyosarcoma of human and rat origin. Am J Pathol 118:246–251
Bandman E (1985a) Myosin isozyme transitions in muscle development, maturation and disease. Int Rev Cytol 97:97–131
Bandman E (1985b) Continued expression of neonatal myosin heavy chain in adult dystrophic skeletal muscle. Science 227:780–782
Caplan AI, Fiszman MY, Eppenberger HM (1983) Molecular and cell isoforms during development. Science 221:921–927
Carlson BM (1973) The regeneration of skeletal muscle. A review. Am J Anat 137:119–150
Chieco-Bianchi L, Collavo D (1976) Some illustrative systems of viral carcinogenesis: (3) the leukemia-sarcoma virus complex in the mouse. In: Symington T, Carter RL (eds) Scientific foundations in oncology. W. Heineman Medical Books, London, pp 388–393
Colombatti A, Collavo D, Biasi G, Chieco-Bianchi L (1975) Genetic control of oncogenesis by murine sarcoma virus Moloney pseudo-type I. Genetics of resistance in AKR mice. Int J Cancer 16:427–434
Cossu G, Molinaro M (1987) Cell heterogenity in the myogenic lineage. Curr Top Dev Biol (in press)
Falcone G, Boettiger D, Alemà S, Tatò F (1984) Role of cell division in differentiation of myoblast infected with temperature-sensitive mutant of Rous sarcoma virus. EMBO J 3:1327–1331
Falcone G, Tatò F, Alemà S (1985) Distinctive effects of the viral oncogenes myc, erb, fps and src on the differentiation program of quail myogenic cells. Proc Natl Acad Sci USA 82:426–432
Fitzsimons RB, Hoh JFY (1981) Embryonic and foetal myosins in human skeletal muscle. The presence of foetal myosin in Duchenne muscular dystrophy and infantile spinal muscular atrophy. J Neurol Sci 52:367–384
Gauthier G, Lowey S (1979) Distribution of myosin isoenzymes among skeletal muscle fiber types. J Cell Biol 81:10–25
Hartley JW, Rowe WP (1975) Clonal cell lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology 65:128–134
Hildebrand HF, Kerckaert JP, Biserte G, Tetaert D, Grandier-Vazaille X (1980) Tumoral myosins of Ni3S2-induced rhabdomyosarcomas in rat and rabbit: comparative studies with adult and fetal myosins of skeletal muscle. Eur J Cell Biol 20:240–248
Izumo S, Nadal-Ginard B, Mahdavi V (1986) All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science 231:597–600
Lasneret J (1967) Etudes des tumeurs provoquée chez le rat par le virus du sarcome de Moloney. Bull Cancer 54:193–200
Levy JP, LeClerc JC (1977) The murine sarcoma virus-induced tumor: exception or general model in tumor immunology? Adv Cancer Res 24:1–66
Lowey S, Risby D (1971) Light chains from fast and slow muscle myosins. Nature 234:81–85
Nanni P, Schiaffino S, DeGiovanni C, Nicoletti G, Prodi G, Del Re B, Eusebi V, Ceccarelli C, Saggin L, Lollini PL (1986) RMZ: a new cell line expression of embryonic myosin. Br J Cancer 54:1009–1014
Nguyen HT, Gubits RM, Wydro RM, Nadal-Ginard B (1982) Sarcomeric myosin heavy chain is coded by a highly conserved multigene family. Proc Natl Acad Sci USA 79:5230–5234
Papkoff J, Verma IM, Hunter T (1982) Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell 29:417–426
Papkoff J, Higg EA, Hunter T (1983) The transformation protein of Moloney murine sarcoma virus is a soluble cytoplasmic protein. Cell 33:161–172
Perk K, Shachat DA, Moloney JB (1968) Pathogenesis of a rhabdomyosarcoma (undifferentiated type) in rats induced by a murine sarcoma virus (Moloney). Cancer Res 28:1197–1206
Pette D, Vrbovà G (1985) Neural control of phenotypic expression in mammalian muscle fibers. Muscle Nerve 8:676–689
Pierobon-Bormioli S, Sartore S, Vitadello M, Schiaffino S (1980) Slow myosins in vertebrate skeletal muscle. J Cell Biol 85:672–681
Pierobon-Bormioli S, Sartore S, Dalla Libera L, Vitadello M, Schiaffino S (1981) Fast isomyosins and fiber types in mammalian skeletal muscle. J Histochem Cytochem 29:1179–1188
Sartore S, Gorza L, Schiaffino S (1982) Fetal myosin heavy chain in regenerating muscle. Nature 298:294–296
Schiaffino S, Gorza L, Dones I, Cornelio F, Sartore S (1985) Fetal myosin immunoreactivity in human dystrophic muscle. Muscle Nerve 8:173–180
Schiaffino S, Gorza L, Sartore S, Saggin L, Carli M (1986) Embryonic myosin heavy chain as a differentiation marker of developing human skeletal muscle and rhabdomyosarcoma. A monoclonal antibody study. Exp Cell Res 163:211–222
Whalen RG (1985) Myosin isoenzymes as molecular markers for muscle physiology. J Exp Biol 115:43–53
Whalen RG, Butler-Browne GS, Gros F (1978) Identification of a novel form of myosin light chain present in embryonic muscle tissue and cultured muscle cells. J Mol Biol 126:415–431
Whalen RG, Schwartz K, Bouveret P, Sell SM, Gros F (1979) Contractile protein isozymes in muscle development: identification of an embryonic form of myosin heavy chain. Proc Natl Acad Sci USA 76:5197–5201
Whalen RG, Sell SM, Butler-Browne GS, Schwartz K, Bouveret P, Pinset-Harstrom I (1981) Three myosin heavy chain isozymes appear sequentially in rat muscle development. Nature 292:805–809
Whalen RG, Toutant M, Butler-Browne GS, Watkins SC (1985) Hereditary pituitary dwarfism in mice affects skeletal and cardiac myosin isozyme transitions differently. J Cell Biol 101:603–609
Wiczoreck DF, Periasamy M, Butler-Browne GS, Whalen RG, Nadal-Ginard B (1985) Co-expression of multiple myosin heavy chain genes, in addition to a tissue specific one, in extrocular muscle. J Cell Biol 101:618–629
Wydro R, Nguyen HT, Gubits R, Nadal-Ginard B (1980) Sarcomeric myosin heavy chain is coded by a highly conserved multigene family. Proc Natl Acad Sci USA 79:5230–5238
Yaffe D, Gershon D (1967) Multinucleated muscle fibers: Induction of DNA synthesis and mitosis by polyoma virus infection. Nature 215:421–424
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Supported in part by grants from CNR (Special Project MPR, SP3, grant no. 83.02823.56; Special Project Oncology, grants no. 84.00495.44 and no. 85.02093.44), Ministero Pubblica Istruzione, and Associazione Italiana Ricerca Cancro
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Azzarello, G., Sartore, S., Saggin, L. et al. Myosin isoform expression in rat rhabdomyosarcoma induced by Moloney murine sarcoma virus. J Cancer Res Clin Oncol 113, 417–429 (1987). https://doi.org/10.1007/BF00390035
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DOI: https://doi.org/10.1007/BF00390035