FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas.
Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in the same samples. The frequency of FasL detection was 30-40% in T and was 60-100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms.
Mann
B
B
Department of General Surgery, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Gratchev
A
A
Böhm
C
C
Hanski
M L
ML
Foss
H D
HD
Demel
G
G
Trojanek
B
B
Schmidt-Wolf
I
I
Stein
H
H
Riecken
E O
EO
Buhr
H J
HJ
Hanski
C
C
D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger