CD74 Promotes a Pro-Inflammatory Tumor Microenvironment by Inducing S100A8 and S100A9 Secretion in Pancreatic Cancer

Sep 24, 2026

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Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, and robust prognostic and predictive biomarkers are still limited. This study examines the molecular role of the receptor CD74 in PDAC, using CD74 silencing in Capan-1 cells. CD74 knockdown suppresses proliferation, migration, and invasion while increasing apoptosis, and it reduces both expression and secretion of S100A8 and S100A9. Conditioned-media co-culture shows lowered inflammatory cytokines, supporting CD74 involvement in shaping the tumor microenvironment. Overall, CD74 is highlighted as a potential diagnostic biomarker and therapeutic target.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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1. Introduction

Article CD74 Promotes a Pro-Inﬂammatory Tumor Microenvironment by Inducing S100A8 and S100A9 Secretion in Pancreatic Cancer Woosol Chris Hong 1,†, Da Eun Lee 2,†, Hyeon Woong Kang 2,3, Myeong Jin Kim 2,3, Minsoo Kim 2,3, Ju Hyun Kim 1, Sungsoon Fang 1, Hyo Jung Kim 1,2,* and Joon Seong Park 1,2, * Citation: Hong, W.C.; Lee, D.E.; Kang, H.W.; Kim, M.J.; Kim, M.; Kim, J.H.; Fang, S.; Kim, H.J.; Park, J.S. CD74 Promotes a Pro-Inﬂammatory Tumor Microenvironment by Inducing S100A8 and S100A9 Secretion in Pancreatic Cancer. Int. J. Mol. Sci. 2023, 24, 12993. [https://](https://) [doi.org/10.3390/ijms241612993](doi.org/10.3390/ijms241612993)[ ](doi.org/10.3390/ijms241612993)Academic Editor: Karel Smetana, Jr. Received: 18 July 2023 Revised: 16 August 2023 Accepted: 17 August 2023 Published: 20 August 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; [chrish95@gmail.com](chrish95@gmail.com) (W.C.H.); [juhyun9503@gmail.com](juhyun9503@gmail.com) (J.H.K.); [sfang@yuhs.ac](sfang@yuhs.ac) (S.F.) 2 Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea; [hsgtj06321@gmail.com](hsgtj06321@gmail.com) (D.E.L.); [kanghw9305@gmail.com](kanghw9305@gmail.com) (H.W.K.); [audwls8739@gmail.com](audwls8739@gmail.com) (M.J.K.); [alstndi777@gmail.com](alstndi777@gmail.com) (M.K.) 3 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea * [Correspondence: hjkim17@yuhs.ac](Correspondence: hjkim17@yuhs.ac) (H.J.K.); [jspark330@yuhs.ac](jspark330@yuhs.ac) (J.S.P.)† These authors contributed equally to this work. Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer with a poor prognosis and low survival rates. The prognostic and predictive biomarkers of PDACare still largely unknown. The receptor CD74 was recently identiﬁed as a regulator of oncogenic properties in various cancers. However, the precise molecular mechanism of CD74 action in PDAC remains little understood. We investigated the role of CD74 by silencing CD74 in the pancreatic cancer cell line Capan-1 . CD74 knockdown led to reductions in cell proliferation, migration, and invasion and increased apoptosis. Moreover, silencing CD74 resulted in the decreased expression and secretion of S100A8 and S100A9 . An indirect co-culture of ﬁbroblasts and tumor cells revealed that ﬁbroblasts exposed to conditioned media from CD74 knockdown cells exhibited a reduced expression of inﬂammatory cytokines, suggesting a role of CD74 in inﬂuencing cytokine secretion in the tumor microenvironment. Overall, our study provides valuable insights into the critical role of CD74 in regulating the oncogenic properties of pancreatic cancer cells and its inﬂuence on the expression and secretion of S100A8 and S100A9 . Taken together, these ﬁndings indicate CD74 as a potential diagnostic biomarker and therapeutic target for pancreatic cancer. Keywords: PDAC; CD74; inﬂammation; ﬁbroblasts; tumor microenvironment 1. Introduction Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer characterized by a poor prognosis and high mortality rates. Despite improvements in treatments, the incidence of pancreatic cancer is increasing, and it is ranked the seventh leading cause of cancer deaths worldwide [1,2] . Approximately 80–85% of pancreatic cancers are determined asunresectable at the time of diagnosis, contributing to the low patient survival rates [3] . In addition, PDAC is associated with a high metastatic capacity to

FAQs

What question does the study address about CD74 in pancreatic cancer?

It investigates how CD74 contributes to the tumor microenvironment in pancreatic ductal adenocarcinoma and why its mechanism is still poorly understood.

What happens to pancreatic cancer cells after CD74 knockdown?

CD74 knockdown reduces cell proliferation, migration, and invasion and increases apoptosis in the Capan-1 pancreatic cancer cell line.

How is CD74 linked to S100A8 and S100A9 and inflammatory signaling?

Silencing CD74 decreases the expression and secretion of S100A8 and S100A9, and conditioned-media co-culture reduces inflammatory cytokine expression in fibroblasts, indicating CD74 shapes cytokine secretion in the tumor microenvironment.

Sep 24, 2026

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