Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment
The complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/2986 |
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| author | Jolimar Hanna Franck Ah-Pine Chailas Boina Yosra Bedoui Philippe Gasque Axelle Septembre-Malaterre |
| author_facet | Jolimar Hanna Franck Ah-Pine Chailas Boina Yosra Bedoui Philippe Gasque Axelle Septembre-Malaterre |
| author_sort | Jolimar Hanna |
| collection | DOAJ |
| description | The complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant mouse (Mo) C3a (rC3a) was produced in CHO cells transfected with a Mo-IL10-signal peptide-Mo C3a plasmid construct. The effects of rC3a, IFN-γ, TGF-β1, and LPS were tested on the expression of C3, C3aR, PI3K, cytokines, chemokines, transcription factors, antioxidant defense mechanisms, angiogenesis and macrophage polarization (M1/M2). 3T3-L1 expressed the highest levels of C3, while C3aR was expressed more by RB. Interestingly, expression of C3/3T3-L1 and C3aR/RB was markedly upregulated by IFN-γ. rC3a was found to upregulate the expression of anti-inflammatory cytokines (IL-10) on 3T3-L1 and TGF-β1 on RB. rC3a also upregulated the expression of pro-inflammatory cytokines in RB. The expression of CCL-5 increased in 3T3-L1 in response to rC3a. On RB, rC3a did not alter M1/M2 polarization but upregulated the expression of antioxidant defense genes, HO-1, and VEGF. C3/C3a produced mainly by MSC may play a critical role in TME remodeling by stimulating both anti-inflammatory and proangiogenic activities of tumor stromal cells. |
| first_indexed | 2024-03-11T03:10:39Z |
| format | Article |
| id | doaj.art-8a063c489cb843a39a077edadcc20557 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:39Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8a063c489cb843a39a077edadcc205572023-11-18T07:39:12ZengMDPI AGCancers2072-66942023-05-011511298610.3390/cancers15112986Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor MicroenvironmentJolimar Hanna0Franck Ah-Pine1Chailas Boina2Yosra Bedoui3Philippe Gasque4Axelle Septembre-Malaterre5Unité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceUnité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceUnité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceUnité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceUnité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceUnité de Recherche EPI (Études Pharmaco-Immunologiques), Université de La Réunion, Allée des Topazes, 97405 Saint-Denis, FranceThe complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant mouse (Mo) C3a (rC3a) was produced in CHO cells transfected with a Mo-IL10-signal peptide-Mo C3a plasmid construct. The effects of rC3a, IFN-γ, TGF-β1, and LPS were tested on the expression of C3, C3aR, PI3K, cytokines, chemokines, transcription factors, antioxidant defense mechanisms, angiogenesis and macrophage polarization (M1/M2). 3T3-L1 expressed the highest levels of C3, while C3aR was expressed more by RB. Interestingly, expression of C3/3T3-L1 and C3aR/RB was markedly upregulated by IFN-γ. rC3a was found to upregulate the expression of anti-inflammatory cytokines (IL-10) on 3T3-L1 and TGF-β1 on RB. rC3a also upregulated the expression of pro-inflammatory cytokines in RB. The expression of CCL-5 increased in 3T3-L1 in response to rC3a. On RB, rC3a did not alter M1/M2 polarization but upregulated the expression of antioxidant defense genes, HO-1, and VEGF. C3/C3a produced mainly by MSC may play a critical role in TME remodeling by stimulating both anti-inflammatory and proangiogenic activities of tumor stromal cells.https://www.mdpi.com/2072-6694/15/11/2986tumoranaphylatoxin C3acomplementtumor microenvironment |
| spellingShingle | Jolimar Hanna Franck Ah-Pine Chailas Boina Yosra Bedoui Philippe Gasque Axelle Septembre-Malaterre Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment Cancers tumor anaphylatoxin C3a complement tumor microenvironment |
| title | Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment |
| title_full | Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment |
| title_fullStr | Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment |
| title_full_unstemmed | Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment |
| title_short | Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment |
| title_sort | deciphering the role of the anaphylatoxin c3a a key function in modulating the tumor microenvironment |
| topic | tumor anaphylatoxin C3a complement tumor microenvironment |
| url | https://www.mdpi.com/2072-6694/15/11/2986 |
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