ORIGINAL PAPER
LAMA1 derived from colorectal cancer promotes M2 polarization in macrophages via activation of EGFR/AKT/CREB pathway
1
Department of Colorectal and Anal Surgery
Affiliated Jinhua Hospital, Zhejiang University School of Medicine
Submission date: 2024-09-20
Final revision date: 2024-11-18
Acceptance date: 2024-11-25
Online publication date: 2025-10-20
Corresponding author
Xihan Jin
Department of Colorectal and Anal Surgery Affiliated Jinhua Hospital, Zhejiang University School of Medicine
Department of Colorectal and Anal Surgery Affiliated Jinhua Hospital, Zhejiang University School of Medicine
Cent Eur J Immunol 2025;(3):234-247
KEYWORDS
ABSTRACT
Background: Although the development of different malignancies is linked to aberrant expression of LAMA1, it is yet unknown how precisely LAMA1 regulates macrophage M2 polarization and the malignant evolution of colorectal cancer (CRC).
Methods: qRT-PCR and western blot (WB) were used to identify the expression of LAMA1 in human normal colonic epithelial cells (NCM-460) and CRC cell lines (RKO, LoVo). Using ELISA kits, the protein levels of LAMA1, IL-10, and Arg1 were determined. The assays used in the study included flow cytometry to evaluate CRC cell apoptosis and macrophage M2 polarization. Colony formation assessed the proliferative ability of co-cultured CRC cells, with Transwell assessing migration and invasion. WB identified the expression of proteins linked to the epithelial-mesenchymal transition (EMT).
Results: In CRC cells, LAMA1 was overexpressed. LAMA1 generated from CRC stimulated the EGFR/AKT/CREB signaling pathway in macrophages to induce M2 polarization of macrophages and eventually promote CRC cell proliferation, migration, and invasion, as well as activate the EMT process and block CRC cell apoptosis.
Conclusion: As a pro-carcinogenic factor released by CRC cells, LAMA1 affects the activation of the EGFR/AKT/CREB pathway in macrophages, causing M2 polarization and aggravating the metastasis and malignant evolution of CRC.
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| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
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