Inhibition of rhabdomyosarcoma's metastatic behavior through downregulation of MET receptor signaling.
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma usually diagnosed in children. In advanced and metastatic stages the prognosis is often poor. RMS cell lines were used for evaluation of the role of MET receptor inhibition on chemotaxis and invasion. In vivo studies were performed using NOD-SCID xenograft model. This study shows that blocking of MET expression has strong influence on metastatic behavior of RMS. MET negative cells possess a reduced potential to migrate and to invade. Downregulation of MET suppressed the ability of RMS cells to populate bone marrow. Inhibition of MET negative tumor cells engraftment into bone marrow was observed. MET negative tumors were also two to four times smaller than their wild type counterparts. Since MET receptor plays a very important role in facilitating metastasis of RMS cells, blocking of HGF-MET axis might be considered as a therapeutic option for RMS patients, at more advanced and metastatic stages.
Lukasiewicz
Ewa
E
Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
Miekus
Katarzyna
K
Kijowski
Jacek
J
Drabik
Grazyna
G
Wilusz
Miroslawa
M
Bobis-Wozowicz
Sylwia
S
Majka
Marcin
M
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D019859:Proto-Oncogene Proteins c-met