TY - JOUR
T1 - The interplay between innate immunity (TLR-4) and sCD40L in the context of an animal model of colitis-associated cancer
AU - Angelou, Anastasios
AU - Papalois, Apostolos E.
AU - Antoniou, Efstathios
AU - Wang, Jaeyun
AU - Amini, Neda
AU - Pikouli, Anastasia
AU - Andreatos, Nikolaos
AU - Buettner, Stefan
AU - Munir, Muhammad
AU - Theodoropoulos, Georgios
AU - Zografos, Georgios C.
AU - Sarantis, Panagiotis
AU - Pulvirenti, Alessandra
AU - Kamphues, Carsten
AU - Theocharis, Stamatios
AU - Pikoulis, Emmanouil
AU - Margonis, Georgios Antonios
N1 - Publisher Copyright:
© 2020 International Institute of Anticancer Research. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - Background/Aim: Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Materials and methods: Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. Results: All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Conclusion: Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer.
AB - Background/Aim: Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Materials and methods: Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. Results: All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Conclusion: Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer.
KW - AOM/DSS
KW - Animal model
KW - Carcinogenesis
KW - Colitis associated cancer
KW - Colorectal cancer
KW - IBD
UR - http://www.scopus.com/inward/record.url?scp=85092121432&partnerID=8YFLogxK
U2 - 10.21873/anticanres.14556
DO - 10.21873/anticanres.14556
M3 - Article
C2 - 32988867
AN - SCOPUS:85092121432
SN - 0250-7005
VL - 40
SP - 5457
EP - 5462
JO - Anticancer research
JF - Anticancer research
IS - 10
ER -