TY - JOUR
T1 - Novel heavily fucosylated glycans as a promising therapeutic target in colorectal cancer
AU - Tsai, Kuei-Yen
AU - Chang, Yu-Jia
AU - Huang, Chien-Yu
AU - Prince, G M Shazzad Hossain
AU - Chen, Hsin-An
AU - Makondi, Precious Takondwa
AU - Shen, Ying-Rou
AU - Wei, Po-Li
N1 - © 2023. The Author(s).
PY - 2023/7/26
Y1 - 2023/7/26
N2 - BACKGROUND: Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear.METHODS: This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model.RESULTS: Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth.CONCLUSIONS: As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.
AB - BACKGROUND: Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear.METHODS: This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model.RESULTS: Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth.CONCLUSIONS: As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.
KW - Humans
KW - Animals
KW - Mice
KW - Neoplasm Recurrence, Local
KW - Immunohistochemistry
KW - Antigens
KW - Disease Models, Animal
KW - Epitopes
KW - Polysaccharides/pharmacology
KW - Colorectal Neoplasms/pathology
KW - Cell Line, Tumor
U2 - 10.1186/s12967-023-04363-5
DO - 10.1186/s12967-023-04363-5
M3 - Article
C2 - 37496011
SN - 1479-5876
VL - 21
SP - 505
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
ER -
