CD95 and TNFα-induced apoptosis in liver metastases of colorectal carcinoma.
BACKGROUND
Therapeutic options in patients with metastatic colorectal cancer are still limited. As apoptosis contributes to the overall sensitivity to radiotherapy or chemotherapy, a better understanding of the apoptotic process in metastatic tumour tissues is necessary.


METHODS
Precision cut tissue slices (PCTS) of three human liver metastases were used to investigate the effect of activating CD95 antibodies (concentrations: 0.1 μg/ml, 1 μg/ml and 1 μg/ml and 1 μg/ml actinomycin D) as well as TNFα (concentrations 1 ng/ml; 10 ng/ml and 10 ng/ml and 1 μg/ml actinomycin D) directly in tumour tissue after 6 h, 12 h and 24 h. The apoptotic effect was assessed immunohistochemically.


RESULTS
Activating CD95 antibodies combined with actino-mycin D led to a significant increase in apoptosis after 12 h. Using TNFα at a high dosage, a significant increase in the apoptosis rate was observed after 6 h and after 12 h in all dosage groups.


CONCLUSIONS
PCTS can be used to investigate the effect of different apoptotic signals directly in human tumour tissues. TNFα is able to effectively induce apoptosis in liver metastases of colorectal carcinoma. Thus, the extrinsic pathway of apoptosis may be a promising target in the development of new therapeutic approaches.
Institut für Pathologie, Medical Center am Clemenshospital, Düesberweg 128, D-48153 Münster, Germany. email@patho-muenster.de
Hans-Udo
HU
Kasper
Elisabeth
E
Konze
Michael
M
Kern
Dirk Ludger
DL
Stippel
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D003609:Dactinomycin / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008867:Microtomy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000906:Antibodies; C491901:FAS protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003609:Dactinomycin