|
|
|
|
|
|
|
||
Articles |
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030
Apoptosis induced by Fas (CD95) ligation is frequently lost during tumor progression; however, there is no direct evidence to support an association of Fas loss-of-function with metastatic tumor behavior. To determine whether Fas loss-of-function is critical for acquisition of the metastatic phenotype, we have compared the ability of Fas-sensitive K1735 murine melanomas to form spontaneous lung metastases in wild-type and Fas ligand–deficient mice. Fas-sensitive melanoma clones are highly tumorigenic but rarely metastatic in wild-type syngeneic mice. However, in Fas ligand–deficient mice, both the incidence and number of metastases are increased. These findings provide the first evidence that Fas–Fas ligand interactions can suppress metastasis and that tumor Fas loss-of-function may be causally linked to metastatic progression.
Key Words: Fas ligand • metastasis • melanoma • apoptosis • lung microenvironment
We would like to acknowledge and thank C.F. Ware (La Jolla Institute for Allergy and Immunology, La Jolla, CA) for providing Fas-Fc and LTβR-Fc; C.D. Bucana for providing expert advice with immunohistochemistry; G. Kiriakova and E. Kruzel for technical assistance; Karen Rameriz for providing technical expertise with flow cytometric analyses; and K. Dunner for assistance with photography.
K.L. van Golen's present address is Department of Internal Medicine, The University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109.
Abbreviations used: FasL, Fas ligand; LCM, lung-conditioned medium.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| TABLE OF CONTENTS |
|
