FADD protein release mirrors the development and aggressiveness of human non-small cell lung cancer.
BACKGROUND
The need to unfold the underlying mechanisms of lung cancer aggressiveness, the deadliest cancer in the world, is of prime importance. Because Fas-associated death domain protein (FADD) is the key adaptor molecule transmitting the apoptotic signal delivered by death receptors, we studied the presence and correlation of intra- and extracellular FADD protein with development and aggressiveness of non-small cell lung cancer (NSCLC).


METHODS
Fifty NSCLC patients were enrolled in this prospective study. Intracellular FADD was detected in patients' tissue by immunohistochemistry. Tumours and distant non-tumoural lung biopsies were cultured through trans-well membrane in order to analyse extracellular FADD. Correlation between different clinical/histological parameters with level/localisation of FADD protein has been investigated.


RESULTS
Fas-associated death domain protein could be specifically downregulated in tumoural cells and FADD loss correlated with the presence of extracellular FADD. Indeed, human NSCLC released FADD protein, and tumoural samples released significantly more FADD than non-tumoural (NT) tissue (P=0.000003). The release of FADD by both tumoural and NT tissue increased significantly with the cancer stage, and was correlated with both early and late steps of the metastasis process.


CONCLUSIONS
The release of FADD by human NSCLC could be a new marker of poor prognosis as it correlates positively with both tumour progression and aggressiveness.
Centre de Recherche des Cordeliers, Equipe 13, Inserm UMRS, Paris, France.
Y
Y
Cimino
A
A
Costes
D
D
Damotte
P
P
Validire
S
S
Mistou
N
N
Cagnard
M
M
Alifano
J-F
JF
Régnard
G
G
Chiocchia
C
C
Sautès-Fridman
L
L
Tourneur
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005110:Extracellular Space / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies
D014408:Biomarkers, Tumor; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein