scholarly journals The squamous cell carcinoma antigen/SERPINB3 protects cervical cancer cells from chemoradiation by preventing lysoptosis

Author(s):  
Songyan Wang ◽  
Cliff Luke ◽  
Stephen Pak ◽  
Victoria Shi ◽  
LiYun Chen ◽  
...  

Abstract The endogenous lysosomal cysteine protease inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) is elevated in patients with cervical cancer and other malignancies. High serum SERPINB3 is prognostic for recurrence and death following chemoradiation therapy (CRT). Cervical cancer cells genetically lacking SERPINB3 are more sensitive to ionizing radiation (IR), suggesting this protease inhibitor plays a role in therapeutic response. Here we demonstrate that SERPINB3-deficient cells have enhanced sensitivity to IR-induced cell death. Knock out of SERPINB3 sensitizes cells to a greater extent than cisplatin, the current standard of care. IR in SERPINB3 deficient cervical carcinoma cells induces cell death morphologically consistent with necrosis, with biochemical and cellular features of lysoptosis. Moreover, rescue with wild-type SERPINB3 or a reactive site loop mutant indicates that protease inhibitory activity is required to protect cervical tumor cells from radiation-induced death. These data suggest targeting of SERPINB3 and lysoptosis to treat radioresistant cervical cancers.

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Songyan Wang ◽  
Cliff J. Luke ◽  
Stephen C. Pak ◽  
Victoria Shi ◽  
Liyun Chen ◽  
...  

AbstractThe endogenous lysosomal cysteine protease inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) is elevated in patients with cervical cancer and other malignancies. High serum SERPINB3 is prognostic for recurrence and death following chemoradiation therapy. Cervical cancer cells genetically lacking SERPINB3 are more sensitive to ionizing radiation (IR), suggesting this protease inhibitor plays a role in therapeutic response. Here we demonstrate that SERPINB3-deficient cells have enhanced sensitivity to IR-induced cell death. Knock out of SERPINB3 sensitizes cells to a greater extent than cisplatin, the current standard of care. IR in SERPINB3 deficient cervical carcinoma cells induces predominantly necrotic cell death, with biochemical and cellular features of lysoptosis. Rescue with wild-type SERPINB3 or a reactive site loop mutant indicates that protease inhibitory activity is required to protect cervical tumor cells from radiation-induced death. Transcriptomics analysis of primary cervix tumor samples and genetic knock out demonstrates a role for the lysosomal protease cathepsin L in radiation-induced cell death in SERPINB3 knock-out cells. These data support targeting of SERPINB3 and lysoptosis to treat radioresistant cervical cancers.


RSC Advances ◽  
2020 ◽  
Vol 10 (49) ◽  
pp. 29156-29170
Author(s):  
Ji Xia ◽  
Yifan Liu ◽  
Menglin Ran ◽  
Wenbo Lu ◽  
Liyan Bi ◽  
...  

Based on SERS-based lateral flow immunoassay, nano-Ag polydopamine nanospheres was used for detecting squamous cell carcinoma antigen and cancer antigen 125 simultaneously in cervical cancer serum.


2005 ◽  
Vol 15 (4) ◽  
pp. 630-638 ◽  
Author(s):  
I. Ogino ◽  
H. Nakayama ◽  
T. Kitamura ◽  
N. Okamoto ◽  
T. Inoue

The objective of this study was to examine the clinical benefits of routine squamous cell carcinoma antigen (SCC-ag) monitoring of patients with locally advanced cervical cancer. Recurrent disease occurred in 99 uterine cervical cancer patients with elevated pretreatment SCC-ag before primary radiotherapy. Elevated SCC-ag levels persisted in 23 patients after primary radiotherapy (group 1), and SCC-ag was normalized in 76 patients after primary radiotherapy (group 2). The overall survival (OS) rate was higher for patients with SCC-ag elevation as the first sign than for patients with recurrence predicted by other modalities for group 2 patients (P = 0.033). The prediction of isolated para-aortic node recurrence significantly correlated with SCC-ag elevation as an initial sign (P = 0.001). The SCC-ag level before primary radiotherapy (≥10.8 ng/mL) significantly affected recurrence predicted by SCC-ag elevation as an initial sign (P = 0.002). For multivariate analysis, the presence of para-aortic node recurrence was statistically significant in OS (P < 0.0001). Routine SCC-ag monitoring of patients with carcinoma of the uterine cervix can lead to the early diagnosis of isolated para-aortic lymph node recurrence, and prolonged survival can be achieved by applying radiation therapy to the para-aortic region. To reduce the number of patients monitored for SCC-ag, we recommend monitoring group 2 patients with pretreatment SCC-ag level before primary radiotherapy ≥10.8 ng/mL.


2019 ◽  
Vol 11 (21) ◽  
pp. 2809-2818 ◽  
Author(s):  
Dan Lu ◽  
Ji Xia ◽  
Zhuo Deng ◽  
Xiaowei Cao

In this study, a highly specific, sensitive and reliable immunosensor has been developed for the quantitative detection of the squamous cell carcinoma antigen (SCCA) in cervical cancer, based on surface-enhanced Raman scattering (SERS).


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