RT Journal Article
SR Electronic
T1 The Complement C3a–C3a Receptor Axis Regulates Epithelial-to-Mesenchymal Transition by Activating the ERK Pathway in Pancreatic Ductal Adenocarcinoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1207
OP 1215
DO 10.21873/anticanres.15587
VO 42
IS 3
A1 REI SUZUKI
A1 YOSHINORI OKUBO
A1 TADAYUKI TAKAGI
A1 MITSURU SUGIMOTO
A1 YUKI SATO
A1 HIROKI IRIE
A1 JUN NAKAMURA
A1 MIKA TAKASUMI
A1 TSUNETAKA KATO
A1 MINAMI HASHIMOTO
A1 RYOUICHIRO KOBASHI
A1 TAKUTO HIKICHI
A1 HIROMASA OHIRA
YR 2022
UL http://ar.iiarjournals.org/content/42/3/1207.abstract
AB Background: We aimed to clarify the role of complement C3a and its receptor C3aR in progression of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: We evaluated the serum levels of C3 and C3a in patients with PDAC. C3aR expression in tissue was assessed using a tissue microarray. To confirm the protumoral effects of C3a in PDAC, we conducted in vitro experiments using PDAC cell lines (Panc-1 and MiaPaca-2) that exhibit high C3aR expression. Results: Serum levels of both C3 and C3a were higher in 26 patients with PDAC than in 28 nontumor-bearing controls. In the tissue microarray, we observed increased expression of C3aR in PDAC cells, especially in cases with metastatic lesions. In vitro experiments showed that C3a facilitated tumor cell proliferation, migration and invasion by activating the extracellular-regulated kinase signaling pathway and inducing epithelial-to-mesenchymal transition. Inhibition of the C3a-C3aR axis by pharmacological blockade and short-hairpin RNA-mediated knockdown of C3aR alleviated its protumoral effect. Conclusion: These findings provide a new approach for the development of treatments targeting the C3a–C3aR axis.