Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Giovanni, Carla De; Lollini, Pier‐Luigi; Dolcetti, Riccardo; Landuzzi, Lorena; Nicoletti, Giordano; D’Andrea, Emma; Scotland, Kymora B.; Nanni, Patrizia

doi:10.1038/bjc.1993.125

Cited by 18 publications

(10 citation statements)

References 42 publications

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“…Furthermore, disrupting JNK after depleting ILK in ERMS cells led to reductions in proliferation, and disruption of c-Jun activity induced apoptosis ( Figure 6 and Supplemental Figure 11). These findings echo previous studies (22,41) and further indicate that activity of c-Jun is of critical importance in RMS cells.…”

Section: Discussionsupporting

confidence: 76%

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma

et al. 2009

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Introduction Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Despite advances in multimodality therapy, the failure-free survival of patients diagnosed with metastatic RMS remains low, at 25% (1). RMS tumors are believed to arise from committed mesenchymal or myogenic progenitor cells that accumulate genetic damage and fail to terminally differentiate (2). RMS tumors largely belong to 2 different histologic subgroupings: 63% are of embryonal RMS (ERMS) histology, while nearly 20% are of alveolar RMS (ARMS) histology (2). In addition to the morphologic and ultrastructural differences between these 2 tumor histologies, they display distinct clinical profiles. ARMS tumors are more likely to be found in the extremities of older children, while ERMS tumors are more commonly found in the head and neck, trunk, and genitourinary systems of younger children (2). ARMS tumors are further associated with a poorer clinical course, exemplified by a higher incidence of bone marrow and lung metastases and higher mortality rate (2).The molecular differences between ARMS and ERMS tumors have been intensively studied (2). Of ARMS tumors, 70% display chromosomal translocations, fusing the neuromuscular development-associated genes paired box 3 (PAX3) and PAX7 to the PKB/

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Section: Discussionsupporting

confidence: 76%

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma

et al. 2009

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“…For anti-myosin immunofluorescent staining, cultures were induced to differentiate in multiwell chamber slides (Nunclon ® ; Nunc, Inc., Naperville, IL). Immunofluorescent labeling of permeabilized cells was performed as described previously (De Giovanni et al, 1993) using anti-myosin heavy chain monoclonal 47A antibody (courtesy of P. A. Merrifield, University of Western Ontario. London, ON).…”

Section: Myogenic Differentiation Assaymentioning

confidence: 99%

Minimal mutations are required to effect a radical change in function in CEA family members of the Ig superfamily

Naghibalhossaini

Stanners

2004

Journal of Cell Science

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GPI anchorage in the CEA family results in the acquisition of radically different functions relative to TM anchorage, including inhibition of differentiation and anoikis, disruption of tissue architecture and promotion of tumorigenicity. CEA GPI anchors, as determined by the carboxy-terminal exon of CEA, demonstrate biological specificity in their ability to confer these functional changes. CEA family GPI anchorage appears to have evolved twice independently during the primate radiation, in a manner suggestive of evolution from more primitive TM-anchored CEACAM1. We show here that very few mutations in the TM exon of present-day human CEACAM1 are required to give efficient GPI anchorage and the biological specificity of CEA GPI anchors, i.e., to give the differentiation-blocking function of GPI-anchored CEA. Such a change in anchorage could therefore represent a relatively facile means for producing radical change in molecular function of Ig superfamily members during evolution.

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“…Studies in rhabdomyosarcoma tumours, the most frequent soft tissue malignancy in paediatric patients, have shown that the malignant phenotype can be repressed to some degree, and that the tumour cells can be induced to re-enter the differentiation process (Gabbert et al, 1988;Aguanno et al, 1990;Crouch and Helman, 1991;De Giovanni et al, 1993). Few studies have been published on drug-induced myogenic differentiation in rhabdomyosarcoma chemotherapy (Lollini et al, 1989;Crouch et al, 1993;D'Amore et al, 1994;Melguizo et al, 1995Melguizo et al, , 1996.…”

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confidence: 99%

GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells

et al. 1999

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Differentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds were designed and synthesized by structural modifications of 5-fluorouracil, a drug which causes considerable cell toxicity and morbidity, and we evaluated their applicability for differentiation therapy in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, ( RS )-1-{[3-(2-hydroxyethoxy)-1- iso propoxy]propyl}-5-fluorouracil, an active drug which shows low toxicity in vivo and releases acrolein which is an aldehyde with anti-tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses (22.5 μmol l −1 and 45 μmol l −1 ) and induced terminal myogenic differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days. Changes in morphological features and in protein organization indicated re-entry in the pathway of muscular maturation. Moreover, GR-891 increased adhesion capability mediated by the expression of fibronectin, and did not induce overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug resistance. New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumour. 1999 Cancer Research Campaign

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Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Cited by 18 publications

References 42 publications

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma

Minimal mutations are required to effect a radical change in function in CEA family members of the Ig superfamily

GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells

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