Mechanism of counterattack of colorectal cancer cell by Fas/Fas ligand system.
OBJECTIVE
To determine the role of Fas/Fas ligand (FasL) in the immune escape of colon cancer cells.


METHODS
Immunohistochemistry was used to observe the expression of Fas and FasL in the tissues of colon cancer patients. In situ hybridization was used to detect the localization of FasL mRNA expression in cancer tissues. Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay and CD45 staining were performed to detect the apoptosis of tumor-infiltrating lymphocytes (TILs). Co-culture assays of colon cancer cells (SW480) and Jurkat cells (Fas-sensitive cells) were performed to observe the counterattack of colon cancer cells to lymphocytes.


RESULTS
Of 53 cases of colon carcinomas, 23 cases (43.4%) expressed Fas which was significantly lower as compared to the normal colonic mucosa (73.3%, P<0.01), and 45 cases (84.9%) of colon carcinomas expressed FasL, whereas only two cases (3.75%) in normal mucosa expressed FasL. FasL expression in the colon cancer cells was found to be associated with increased cell death of TILs. The apoptotic rate of TIL in the FasL-positive staining regions of tumor cells was significantly higher than that in the FasL-negative staining region (54.84+/-2.79% vs 25.73+/-1.98%, P<0.01). The co-culture of SW480 cells and Jurkat cells confirmed the function of FasL on the SW480 cells. The apoptotic rates of Jurkat cells were found to be related with the amount of SW480 cells.


CONCLUSIONS
Colon cancer cells can escape the immune surveillance and killing via decreasing Fas expression, and can counterattack the immune system via increasing FasL expression. Fas/FasL can serve as potential targets for effective antitumor therapy.
Zhu
Qiang
Q
Department of Gastroenterology, Shandong Provincial Hospital, Jing 5 Wei 7 Road, 324#, Jinan 250021, Shandong Province, China. zhuqiang@medmail.com.cn
Liu
Ji-Yong
JY
Xu
Hong-Wei
HW
Yang
Chong-Mei
CM
Zhang
An-Zhong
AZ
Cui
Yi
Y
Wang
Hong-Bo
HB
D017209:Apoptosis / Q000276:immunology; D002470:Cell Survival; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D019014:fas Receptor