Research Article

Evaluation the Effect of Tumor-Associated Macrophage-Derived Factors on Pancreatic Cancer Microenvironment Cells

Volume: 16 Number: 1 January 1, 2025
EN

Evaluation the Effect of Tumor-Associated Macrophage-Derived Factors on Pancreatic Cancer Microenvironment Cells

Abstract

Purpose: The unique tumor microenvironment (TME) of pancreatic cancer (PCa) is a critical factor contributing to its aggressive and incurable nature. Pancreatic stellate cells (PSCs) are among the most abundant stromal cells in the TME, closely associated with tumor progression, metastasis, and chemo-/radioresistance. Tumor-associated macrophages (TAMs) are another important cell type in the TME, playing a vital role in promoting tumor growth and metastasis. Limited research exists on the interaction between PSCs and TAMs, highlighting the need for more studies to better understand the interaction between these two cell types. Methods: THP-1 monocytic cells were differentiated into macrophages, and differentiation efficacy was confirmed by morphological analysis and Western blot. PSCs were co-cultured with monocytes/macrophages, and changes in the migration and invasion abilities of PSCs were assessed by wound healing and transwell invasion assays, respectively. To investigate the effects of macrophage derived factors, MCP-1 and Gas6, on PSC-macrophage interaction, these proteins were applied to PSCs, or their receptors (Axl and CCR2) were suppressed using siRNA technology. The effects of Gas6/Axl and MCP-1/CCR2 signaling on PSC cell viability, colony formation, and migration were then evaluated. Results: While MCP-1 did not induce changes in colony-forming and migration abilities of PSCs, Gas6 treatment caused an induction. This effect was reduced when the Gas6 receptor Axl was suppressed with siRNA, suggesting Gas6/Axl signaling might play critical role in macrophage-mediated changes in PSCs. Conclusion: Further research is needed to fully understand the interaction between PSCs and TAMs in pancreatic cancer.

Keywords

References

  1. 1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
  2. 2. Ren B, Cui M, Yang G, et al. Tumor microenvironment participates in metastasis of pancreatic cancer. Mol Cancer. 2018;17(1):108.
  3. 3. Murakami T, Hiroshima Y, Matsuyama R, et al. Role of the tumor microenvironment in pancreatic cancer. Ann Gastroenterol Surg. 2019;3(2):130-7.
  4. 4. Karamitopoulou E. Tumour microenvironment of pancreatic cancer: immune landscape is dictated by molecular and histopathological features. Br J Cancer. 2019;121:5-14.
  5. 5. Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut. 1998;43:128-33.
  6. 6. Apte MV, Wilson JS, Lugea A, et al. A starring role for stellate cells in the pancreatic cancer microenvironment, J Gastroenterology. 2013;144:1210-9.
  7. 7. Erkan M. The role of pancreatic stellate cells in pancreatic cancer. Pancreatology. 2013, 13(2):106-9.
  8. 8. Wu Y, Zhang C, Jiang K, et al. The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives. Front Oncol. 2021;10:621937.

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other)

Journal Section

Research Article

Early Pub Date

December 10, 2024

Publication Date

January 1, 2025

Submission Date

August 23, 2024

Acceptance Date

November 21, 2024

Published in Issue

Year 2025 Volume: 16 Number: 1

EndNote
Karakaş D, Dere E, Ulukaya E, Ozpolat B (January 1, 2025) Evaluation the Effect of Tumor-Associated Macrophage-Derived Factors on Pancreatic Cancer Microenvironment Cells. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 16 1 24–31.