Differentiation of rhabdomyosarcoma cell lines using retinoic acid.
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.


OBJECTIVE
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.
Barlow
Jason W
JW
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Wiley
Joe C
JC
Mous
Marieke
M
Narendran
Aru
A
Gee
Matthew F W
MF
Goldberg
Michael
M
Sexsmith
Elizabeth
E
Malkin
David
D
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity; D014212:Tretinoin / Q000494:pharmacology*; D020107:Troponin T / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000970:Antineoplastic Agents; C495901:TP53 protein, human; D020107:Troponin T; D016159:Tumor Suppressor Protein p53; D000077556:Alitretinoin; D000431:Ethanol; D014212:Tretinoin