Conflict of interest: Nothing to declare.
Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts†
Article first published online: 19 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 4, pages 575–579, April 2013
How to Cite
Rao-Bindal, K., Rao, C. K., Yu, L. and Kleinerman, E. S. (2013), Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts. Pediatr. Blood Cancer, 60: 575–579. doi: 10.1002/pbc.24412
- Issue published online: 13 FEB 2013
- Article first published online: 19 DEC 2012
- Manuscript Accepted: 1 NOV 2012
- Manuscript Received: 24 JAN 2012
- National Cancer Institute grant. Grant Number: R01 CA42992
- National Institutes of Health. Grant Number: CA16672
- American Legion Auxiliary
- Fas/FasL pathway;
- pulmonary metastasis
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.
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.
c-FLIP expression was significantly higher in the lung metastases than in the primary tumors.
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. Pediatr Blood Cancer 2013; 60: 575–579. © 2012 Wiley Periodicals, Inc.