title: Radiation therapy may increase metastatic potential in alveolar rhabdomyosarcoma.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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).
authors: Nationwide Children's Hospital, Columbus, OH.
authors: Gary M
authors: GM
authors: Woods
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Kathryn
authors: K
authors: Bondra
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Christopher
authors: C
authors: Chronowski
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Justin
authors: J
authors: Leasure
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Mamata
authors: M
authors: Singh
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Lauren
authors: L
authors: Hensley
authors: Nationwide Children's Hospital, Columbus, OH.
authors: Timothy P
authors: TP
authors: Cripe
authors: Wexner Medical Center at The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, Columbus, OH.
authors: Arnab
authors: A
authors: Chakravarti
authors: Nationwide Children's Hospital, Columbus, OH.
authors: Peter
authors: P
authors: Houghton
mesh_terms: D000008:Abdominal Neoplasms / Q000209:etiology / Q000556:secondary*; D000818:Animals; D001365:Axilla; D019583:Dose Fractionation, Radiation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000556:secondary*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000009:adverse effects*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary*; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000209:etiology / Q000556:secondary; D040521:Subcutaneous Tissue
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: cancer genetics; pediatric oncology; radiation therapy; rhabdomyosarcoma; soft tissue sarcoma