Cultivation in vitro of cells derived from a human rhabdomyosarcoma

McAllister, Robert M.; Melnyk, John; Finklestein, Jerry Z.; Adams, Ernest C.; Gardner, Murray B.

doi:10.1002/1097-0142(196909)24:3<520::aid-cncr2820240313>3.0.co;2-m

Cited by 295 publications

(135 citation statements)

References 11 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Rhabdomyosarcoma is composed of embryonal and alveolar subtypes. KYM-1 and RD is established from embryonal rhabdomyosarcoma (McAllister et al, 1969;Sekiguchi et al, 1985). The subtype of A204 was not described in article of cell line establishment (Giard et al, 1973).…”

Section: Discussionmentioning

confidence: 99%

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: The hypothesis that malignant tumours are generated by rare populations of cancer stem cells that are more tumourigenic than other cancer cells has gained increasing credence. The objective of this study was to identify and characterise a subpopulation of human sarcoma-initiating cells. METHODS: We examined established rhabdomyosarcoma cell lines by flow cytometry. Tumourigenesis was examined by xenograft models. Real-time PCR and immunohistochemistry were performed to examine the gene expression using cell lines and biopsy specimens. RESULTS: Rhabdomyosarcoma cell lines included small populations of fibroblast growth factor receptor 3 (FGFR3)-positive cells. FGFR3-positive KYM-1 and RD cells were more strongly tumourigenic than FGFR3-negative cells. In addition, xenoengraftment of 33% of single FGFR3-positive KYM-1 cells yielded tumour formation. Stem cell properties of FGFR3-positive cells were further established by real-time PCR, which demonstrated upregulation of undifferentiated cell markers and downregulation of differentiation markers. We showed that in the absence of serum, addition of basic fibroblast growth factor maintained and enriched FGFR3-positive cells. On the other hand, ciliary neurotrophic factor reduced the proportion of FGFR3-positive cells. Real-time PCR and immunohistochemical examination revealed that embryonal rhabdomyosarcoma patient biopsy specimens were found to overexpress FGFR3. CONCLUSIONS: Our findings suggest that rhabdomyosarcoma cell lines include a minor subpopulation of FGFR3-positive sarcomainitiating cells, which can be maintained indefinitely in culture and which is crucial for their malignancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In this present study, we further examined the molecular mechanisms that prevent MyoD activity in RMSs, focusing on the RD RMS cell line derived from an embryonal RMS (McAllister et al 1969). We demonstrate that MSC and an inhibitory splice form of E2A compete with MyoD for dimerization with the full-length functional E-proteins, and that establishing a dimer between MyoD and the full-length E-protein is sufficient to broadly suppress inhibitory factors in RMSs and induce terminal differentiation.…”

mentioning

confidence: 94%

MyoD and E-protein heterodimers switch rhabdomyosarcoma cells from an arrested myoblast phase to a differentiated state

et al. 2009

View full text Add to dashboard Cite

Rhabdomyosarcomas are characterized by expression of myogenic specification genes, such as MyoD and/or Myf5, and some muscle structural genes in a population of cells that continues to replicate. Because MyoD is sufficient to induce terminal differentiation in a variety of cell types, we have sought to determine the molecular mechanisms that prevent MyoD activity in human embryonal rhabdomyosarcoma cells. In this study, we show that a combination of inhibitory Musculin:E-protein complexes and a novel splice form of E2A compete with MyoD for the generation of active full-length E-protein:MyoD heterodimers. A forced heterodimer between MyoD and the full-length E12 robustly restores differentiation in rhabdomyosarcoma cells and broadly suppresses multiple inhibitory pathways. Our studies indicate that rhabdomyosarcomas represent an arrested progress through a normal transitional state that is regulated by the relative abundance of heterodimers between MyoD and the full-length E2A proteins. The demonstration that multiple inhibitory mechanisms can be suppressed and myogenic differentiation can be induced in the RD rhabdomyosarcomas by increasing the abundance of MyoD: E-protein heterodimers suggests a central integrating function that can be targeted to force differentiation in muscle cancer cells.[Keywords: E2A; Musculin; MyoD; myogenesis; rhabdomyosarcoma] Supplemental material is available at http://www.genesdev.org.

show abstract

“…The most interesting features of the new human cell line, RMZ, described here are the following: (1) obtained from Duchenne muscular dystrophy patients (Blau et al, 1983) and in two other rhabdomyosarcoma cell lines (McAllister et al, 1969;Chapman et al, 1974). It is possible that the presence of such cells could be related with developmental alterations.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few human rhabdomyosarcoma cell lines have been recently studied (McAllister et al, 1969;Giard et al, 1973;Chapman et al, 1974;McAllister et al, 1975); whenever histologic type is specified, the original tumour was an embryonal rhabdomyosarcoma. Moreover, in vitro differentiation properties of human rhabdomyosarcoma cells have not yet been fully characterized.…”

mentioning

confidence: 99%

RMZ: A new cell line from a human alveolar rhabdomyosarcoma. In vitro expression of embryonic myosin

Nanni¹,

Schiaffino²,

Giovanni³

et al. 1986

Br J Cancer

View full text Add to dashboard Cite

Summary The RMZ cell line was established from a bone marrow metastasis of a human alveolar rhabdomyosarcoma. Since the beginning of the in vitro culture, RMZ cells showed a differentiation-related morphological heterogeneity: actively proliferating polygonal or spindle-shaped cells were observed along with a few multinucleated myotube-like structures and giant cells, frequently multinucleated. All these cell types were still present after over 40 passages. A set of clonal derivatives has been obtained from the second in vitro subculture. All the clones showed the same morphological heterogeneity of the parental cells, but differed from one another in the degree of differentiation.Multinucleated myotube-like structures were strongly stained by anti-desmin antibody; most mononuclear cells were weakly stained. About 80% of RMZ and cloned cells were scored as desmin-positive in cytocentrifuged preparations. The expression of embryonic myosin heavy chain, specifically recognized by the monoclonal antibody BF-G6, was found in RMZ cell line and was localised in the myotube-like structures. Only a few giant cells and rare mononucleated polygonal cells were stained. The average proportion of BF-G6 positive cells in cytocentrifuged preparations was of about 6% of the total RMZ cells. In the two RMZ clones studied, the expression of embryonic myosin was correlated to the proportion of myotube-like structures: a BF-G6 positivity of 35% was found in the most differentiated one.

show abstract

Cultivation in vitro of cells derived from a human rhabdomyosarcoma

Cited by 295 publications

References 11 publications

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

MyoD and E-protein heterodimers switch rhabdomyosarcoma cells from an arrested myoblast phase to a differentiated state

RMZ: A new cell line from a human alveolar rhabdomyosarcoma. In vitro expression of embryonic myosin

Contact Info

Product

Resources

About