Monocytes and Macrophage-derived mediators influence the behavior of squamous cell carcinoma cell lines

Graziela Perri; Raíssa Gabrieli Candido; Luiz Henrique Camargo Soares; Rafael Carneiro Ortiz; Izabel de Camargo; Maria Renata Sales Nogueira; Edgard José Franco Merllo Júnior; Ana Lucia Coelho; Edwin M Posadas; Cory Hogaboam; Karen A Cavassani; Ana Paula Campanelli

doi:10.1590/

Authors

Graziela Perri Universidade de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciências Biológicas https://orcid.org/0000-0002-4937-210X
Raíssa Gabrieli Candido Universidade de São Paulo. Faculdade de Odontologia de Bauru https://orcid.org/0000-0002-2939-7465
Luiz Henrique Camargo Soares Universidade de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciências Biológicas
Rafael Carneiro Ortiz Universidade de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciências Biológicas https://orcid.org/0000-0002-2794-0460
Izabel de Camargo Universidade de São Paulo. Faculdade de Odontologia de Bauru., Departamento de Ciências Biológic
Maria Renata Sales Nogueira Secretaria de Estado da Saúde. Instituto Lauro de Souza Lima https://orcid.org/0000-0001-8647-0350
Edgard José Franco Merllo Júnior Secretaria de Estado da Saúde. Instituto Lauro de Souza Lima
Ana Lucia Coelho Cedars-Sinai Medical Center. Division of Pulmonary and Critical Care Medicine. Department of Medicine https://orcid.org/0000-0001-5087-6842
Edwin M Posadas Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Cory Hogaboam Cedars-Sinai Medical Center. Division of Pulmonary and Critical Care Medicine. Department of Medicine
Karen A Cavassani Cedars-Sinai Medical Center. Samuel Oschin Comprehensive Cancer Institute
Ana Paula Campanelli Universidade de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciências Biológicas https://orcid.org/0000-0002-0536-5469

DOI:

https://doi.org/10.1590/

Keywords:

Macrophage, Monocytes, Squamous cell carcinoma

Abstract

Immune cells play diverse roles in cancer development. Myeloid cells are key drivers of tumor-escape mechanisms as they suppress immune responses, facilitate metastasis, and contribute to therapy resistance. In particular, macrophages can be polarized into an inflammatory M1 (anti-tumor) or anti-inflammatory M2 (pro-tumor) phenotype. M2 macrophages are associated with tumor progression, as they secrete factors that promote tumor angiogenesis, suppress T-cell activity, and correlate with poor clinical outcomes in squamous cell carcinoma (SCC). Given this context, this study aims to demonstrate the biological effects of monocytes and both M1 and M2 macrophages in squamous cell carcinoma. Our data indicate higher CD163 immunoreactivity in biopsies from SCC patients. Furthermore, we found that a conditioned medium (CM) containing bioactive compound generated by M2 macrophages enhances the proliferation and invasion of the SCC-25 cell line in vitro. Surprisingly, CM derived from blood CD14⁺ monocytes increased SCC-25 proliferation at the same rate of M2 macrophages-CM. M1 macrophages conditioned medium significantly enhanced the motility and decreased proliferation in Detroit 562 cells. The analysis of tumor-associated transcripts showed that both M1 and M2 conditioned medium induced high levels of EPCAM mRNA and significantly decreased the expression of MYC, an epithelial-to-mesenchymal transition marker, in SCC cell lines. Detroit cells exposed to conditioned medium from monocytes and macrophage also showed elevated SOX2 mRNA levels. The findings suggest that monocytes and macrophage mediators exert distinct biological effects on SCC cell lines.

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