Abstract
Objective(s): We have previously shown that Fas expression inversely correlates with the metastatic potential of osteosarcoma (OS) to the lung. FasL is constitutively expressed in the lung microenvironment and eliminates Fas+ OS cells leaving Fas- cells to form metastases. Absence of FasL in the lung epithelium or blocking the Fas-signaling pathway interfered with this clearance mechanism allowing Fas+ cells to remain and form lung metastases. We also demonstrated that while the majority of patient OS lung metastases were Fas-, 10-20% of the lesions contained Fas+ cells, suggesting that these cells were not sensitive to FasL-induced apoptosis. The expression of c-FLIP, an inhibitor of the Fas pathway, has been associated with tumor development, progression, and resistance to chemotherapy. We therefore evaluated the expression of c-FLIP in OS patient tumor specimens and human xenograft lung metastases. Methods: OS patient tissues, which included both primary and metastatic lesions, were evaluated for the expression of c-FLIP. In addition, tumors from human OS xenografts were examined for c-FLIP expression. Results: c-FLIP expression was significantly higher in the lung metastases than in the primary tumors. Conclusion(s): c-FLIP may play an important role in the metastatic potential of OS to the lung. Inhibition of c-FLIP may be a future therapeutic target.
Original language | English (US) |
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Pages (from-to) | 575-579 |
Number of pages | 5 |
Journal | Pediatric Blood and Cancer |
Volume | 60 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2013 |
Keywords
- C-FLIP
- Fas/FasL pathway
- Osteosarcoma
- Pulmonary metastasis
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Hematology
- Oncology
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