Research Article
Year 2025,
Issue: Kabul Edilen Makaleler
Abstract
References
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- 2. Ren B, Cui M, Yang G, et al. Tumor microenvironment participates in metastasis of pancreatic cancer. Mol Cancer. 2018;17(1):108.
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- 19. Morizono K, Xie Y, Olafsen T, et al. The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell Host Microbe. 2011;9:286–98.
- 20. Lien MY, Chang AC, Tsai HC, et al. Monocyte Chemoattractant Protein 1 Promotes VEGF-A Expression in OSCC by Activating ILK and MEK1/2 Signaling and Downregulating miR-29c. Front Oncol. 2020;10:592415.
- 21. Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399-416. 22. Lin HJ, Liu Y, Caroland K, Lin J. Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2023;15(13):3507.
- 23. McGuigan AJ, Coleman HG, McCain RS, et al. Immune cell infiltrates as prognostic biomarkers in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. J Pathol Clin Res. 2021;7(2):99-112.
- 24. Chen Y, Lei Y, Li J, et al. Macrophage-derived exosomal microRNAs promote metastasis in pancreatic ductal adenocarcinoma. Int Immunopharmacol. 2024; 129:111590.
- 25. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(3):639-52.
- 26. Yoshimura T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cell Mol Immunol. 2018;15(4):335-45.
- 27. Feng L, Qi Q, Wang P, et al. Serum Level of CCL2 Predicts Outcome of Patients with Pancreatic Cancer. Acta Gastroenterol Belg. 2020;83:295–9.
- 28. Du W, Brekken RA. Does Axl have potential as a therapeutic target in pancreatic cancer? Expert Opin Ther Targets. 2018;22(11):955-66.
- 29. Wu G, Ma Z, Cheng Y et al. Targeting Gas6/TAM in cancer cells and tumor microenvironment. Mol Cancer. 2018;17:20.
- 30. Laurance S, Bertin FR, Ebrahimian T, et al. Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arterioscler Thromb Vasc Biol. 2017;37(7):1315-22.
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.
References
- 1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
- 2. Ren B, Cui M, Yang G, et al. Tumor microenvironment participates in metastasis of pancreatic cancer. Mol Cancer. 2018;17(1):108.
- 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. Karamitopoulou E. Tumour microenvironment of pancreatic cancer: immune landscape is dictated by molecular and histopathological features. Br J Cancer. 2019;121:5-14.
- 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. 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. Erkan M. The role of pancreatic stellate cells in pancreatic cancer. Pancreatology. 2013, 13(2):106-9.
- 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.
- 9. Strizova Z, Benesova I, Bartolini R, et al. M1/M2 macrophages and their overlaps - myth or reality? Clin Sci (Lond). 2023;137(15):1067-93.
- 10. Wang S, Wang J, Chen Z, et al. Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance. NPJ Precis Oncol. 2024;8(1):31.
- 11. Deshmane SL, Kremlev S, Amini S, et al. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009;29(6):313-26.
- 12. Wang L, Lan J, Tang J, Luo N. MCP-1 targeting: Shutting off an engine for tumor development. Oncol Lett. 2022;23(1):26.
- 13. Song X, Wang H, Logsdon CD, et al. Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer. 2011;117:734–43.
- 14. Tanaka M, Siemann DW. Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer. Int J Mol Sci. 2021;22(18):9953.
- 15. Goyette MA, Elkholi IE, Apcher C, et al. Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels. Proc Natl Acad Sci USA. 2021;118(29):e2023868118.
- 16. Sica A. Macrophages give Gas(6) to cancer. Blood. 2010;115(11):2122-3.
- 17. Zhang C, Yang M, Ericsson AC. Function of Macrophages in Disease: Current Understanding on Molecular Mechanisms. Front Immunol. 2021;12:620510.
- 18. Kirane A, Ludwig KF, Sorrelle N, et al. Warfarin Blocks Gas6-Mediated Axl Activation Required for Pancreatic Cancer Epithelial Plasticity and Metastasis. Cancer Res. 2015;75(18):3699-705.
- 19. Morizono K, Xie Y, Olafsen T, et al. The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell Host Microbe. 2011;9:286–98.
- 20. Lien MY, Chang AC, Tsai HC, et al. Monocyte Chemoattractant Protein 1 Promotes VEGF-A Expression in OSCC by Activating ILK and MEK1/2 Signaling and Downregulating miR-29c. Front Oncol. 2020;10:592415.
- 21. Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399-416. 22. Lin HJ, Liu Y, Caroland K, Lin J. Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2023;15(13):3507.
- 23. McGuigan AJ, Coleman HG, McCain RS, et al. Immune cell infiltrates as prognostic biomarkers in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. J Pathol Clin Res. 2021;7(2):99-112.
- 24. Chen Y, Lei Y, Li J, et al. Macrophage-derived exosomal microRNAs promote metastasis in pancreatic ductal adenocarcinoma. Int Immunopharmacol. 2024; 129:111590.
- 25. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(3):639-52.
- 26. Yoshimura T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cell Mol Immunol. 2018;15(4):335-45.
- 27. Feng L, Qi Q, Wang P, et al. Serum Level of CCL2 Predicts Outcome of Patients with Pancreatic Cancer. Acta Gastroenterol Belg. 2020;83:295–9.
- 28. Du W, Brekken RA. Does Axl have potential as a therapeutic target in pancreatic cancer? Expert Opin Ther Targets. 2018;22(11):955-66.
- 29. Wu G, Ma Z, Cheng Y et al. Targeting Gas6/TAM in cancer cells and tumor microenvironment. Mol Cancer. 2018;17:20.
- 30. Laurance S, Bertin FR, Ebrahimian T, et al. Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arterioscler Thromb Vasc Biol. 2017;37(7):1315-22.
There are 29 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Biochemistry and Cell Biology (Other) |
| Journal Section | Clinical Research |
| Authors | |
| Early Pub Date | December 10, 2024 |
| Publication Date | |
| Submission Date | August 23, 2024 |
| Acceptance Date | November 21, 2024 |
| Published in Issue | Year 2025Issue: Kabul Edilen Makaleler |