Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts

Krithi Rao-Bindal, Chethan K. Rao, Ling Yu, Eugenie S. Kleinerman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 languageEnglish (US)
Pages (from-to)575-579
Number of pages5
JournalPediatric Blood and Cancer
Volume60
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • C-FLIP
  • Fas/FasL pathway
  • Osteosarcoma
  • Pulmonary metastasis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

MD Anderson CCSG core facilities

  • Research Animal Support Facility
  • Clinical Trials Office

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