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Radiation therapy may increase metastatic potential in alveolar rhabdomyosarcoma
Author(s) -
Woods Gary M.,
Bondra Kathryn,
Chronowski Christopher,
Leasure Justin,
Singh Mamata,
Hensley Lauren,
Cripe Timothy P.,
Chakravarti Arnab,
Houghton Peter J.
Publication year - 2015
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.25516
Subject(s) - medicine , alveolar rhabdomyosarcoma , rhabdomyosarcoma , radiation therapy , metastasis , in vivo , cancer research , pathology , oncology , cancer , sarcoma , biology , microbiology and biotechnology
Background We previously determined that radiation could be safely administered using a mouse‐flank in vivo model to both alveolar (Rh30) and embryonal (Rh18) rhabdomyosarcoma xenografts. Mice from both tumor lines in this experiment developed metastases, an event not previously described with these models. We sought to determine if radiation‐induced changes in gene expression underlie an increase in the metastatic behavior of these tumor models. Procedure Parental Rh18 and Rh30 xenografts, as well as tumor that recurred locally after radiotherapy (Rh18RT and Rh30RT), were grown subcutaneously in the flanks of SCID mice and then subjected to either fractionated radiotherapy or survival surgery alone. Metastasis formation was monitored and recorded. Gene expression profiling was also performed on RNA extracted from parental, recurrent, and metastatic tissue of both tumor lines. Results Rh30 and Rh30RT xenografts demonstrated metastases only if they were exposed to fractionated radiotherapy, whereas Rh18 and Rh18RT xenografts experienced significantly fewer metastatic events when treated with fractionated radiotherapy compared to survival surgery alone. Mean time to metastasis formation was 40 days in the recurrent tumors and 73 days in the parental xenografts. Gene expression profiling noted clustering of Rh30 recurrent and metastatic tissue that was independent of the parental Rh30 tissue. Rh18RT xenografts lost radiosensitivity compared to parental Rh18. Conclusion Radiation therapy can significantly decrease the formation of metastases in radio‐sensitive tumors (Rh18) and may induce a more pro‐metastatic phenotype in radio‐resistant lines (Rh30). Pediatr Blood Cancer 2015;62:1550–1554. © 2015 Wiley Periodicals, Inc.