Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer.
BACKGROUND
Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls.


METHODS
Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits.


RESULTS
We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer.


CONCLUSIONS
Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the levels of sCD95 in serum could be helpful during the prognosis and treatment of women detected with precancerous lesions or cervical cancer.
Aguilar-Lemarroy
Adriana
A
División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México. adry_al@yahoo.de
Romero-Ramos
Jose E
JE
Olimon-Andalon
Vicente
V
Hernandez-Flores
Georgina
G
Lerma-Diaz
Jose M
JM
Ortiz-Lazareno
Pablo C
PC
Morgan-Villela
Gilberto
G
Del Toro-Arreola
Susana
S
Bravo-Cuellar
Alejandro
A
Jave-Suarez
Luis F
LF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D006801:Humans; D019169:Jurkat Cells / Q000502:physiology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000503:physiopathology*; D019014:fas Receptor / Q000097:blood*; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000503:physiopathology*
D014408:Biomarkers, Tumor; D019014:fas Receptor