Research Paper Volume 16, Issue 10 pp 8880—8897
PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression
- 1 Graduate School, Hebei North University, Zhangjiakou 075000, China
- 2 Department of Ultrasound Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China
- 3 Department of Anus and Intestine Surgery, Tianjin People's Hospital, Tianjin 300122, China
- 4 Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China
- 5 Institute of Tumor, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China
- 6 Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China
Received: September 9, 2023 Accepted: March 13, 2024 Published: May 17, 2024
https://doi.org/10.18632/aging.205847How to Cite
Copyright: © 2024 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways.
Method: Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation.
Results: Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention.
Conclusions: PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.