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Differentiation of rhabdomyosarcoma cell lines using retinoic acid
Author(s) -
Barlow Jason W.,
Wiley Joe C.,
Mous Marieke,
Narendran Aru,
Gee Matthew F.W.,
Goldberg Michael,
Sexsmith Elizabeth,
Malkin David
Publication year - 2006
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20650
Subject(s) - rhabdomyosarcoma , medicine , retinoic acid , cancer research , tretinoin , cell culture , computational biology , pathology , genetics , sarcoma , biology
Background Rhabdomyosarcoma (RMS) is the most frequent sporadic soft tissue sarcoma of childhood and adolescence. The overall 5‐year survival rate for patients with RMS is 70% with the use of surgery, radiation, and chemotherapy. Novel therapeutic approaches are necessary to improve on these outcomes particularly among the more aggressive alveolar RMS (ARMS) and late stages of disease, where 5‐year survival is less than 20%. Retinoids have been successfully used in the treatment of acute promyelocytic leukemia (APML) and neuroblastoma. Purpose However, analysis of retinoids as a differentiating agent for RMS has been incomplete. This work examined the ability of retinoic acid (RA) to promote differentiation of RMS cell lines by examining the expression of myogenic proteins in five RMS cell lines in response to All‐ trans Retinoic Acid (ATRA) or 9‐ cis retinoic acid (CRA). Results Analysis of growth curves indicates that both retinoids suppress cell growth of Rh4 and Rh28. RD cells only responded to‐CRA whereas Rh30 and Rh18 did not respond. Following treatment with ATRA FACS analysis showed an altered cell cycle with the same pattern as the growth curves. ATRA altered cellular morphology of two cell lines, Rh4 and Rh28, and induced Troponin T expression in these cells suggesting a differentiating effect. Conclusions These studies suggest that retinoids are effective inducers of growth arrest and differentiation in some RMS cell lines, and offer a basis for further in vivo testing in mice of ATRA as a potential approach to ARMS treatment. Pediatric Blood Cancer 2006;47:773–784. © 2005 Wiley‐Liss, Inc.