Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression.
BACKGROUND
Tumor-derived membranous vesicles (MV) isolated from sera of the patients with squamous cell carcinomas of the head and neck (HNSCC) induce apoptosis of activated CD8(+) T cells. We tested if MV molecular profile and activity correlate with disease progression.


METHODS
CD8(+) Jurkat cells were incubated with MAGE 3/6(+), FasL(+), MHC class I(+) MV isolated from sera of 60 patients with HNSCC and 25 normal controls by exclusion chromatography and ultracentrifugation. Z-VAD-FITC binding to Jurkat was measured and correlated with clinical data.


RESULTS
MV from patients' sera, but not from sera of normal controls, induced Jurkat cell apoptosis. Forty-five percent T cells+MV from patients with N(1)-N(3) disease were apoptotic versus 18% T cells+MV from patients with N(0) disease (p < .008). MV from patients with active disease (AD) expressed higher FasL levels than MV from patients with no evident disease (NED) or normal controls (p <or= .01).


CONCLUSIONS
MAGE 3/6(+), FasL(+), and MHCI(+) MV in sera of patients induced T-cell apoptosis, which correlated with disease activity and the presence of lymph node metastases.
Bergmann
Christoph
C
Departments of Pathology and Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Strauss
Laura
L
Wieckowski
Eva
E
Czystowska
Malgorzata
M
Albers
Andreas
A
Wang
Yun
Y
Zeidler
Reinhard
R
Lang
Stephan
S
Whiteside
Theresa L
TL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology*; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D018450:Disease Progression; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology*; D006801:Humans; D019169:Jurkat Cells / Q000473:pathology; D008207:Lymphatic Metastasis; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged
D000590:Amino Acid Chloromethyl Ketones; D000951:Antigens, Neoplasm; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases