Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition
ABSTRACT Aim The tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial‐to‐mesenchymal transition...
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| Format: | Article |
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Wiley
2025-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70707 |
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| author | Clara Bourreau Emilie Navarro Marine Cotinat Morgane Krejbich François Guillonneau Catherine Guette Alice Boissard Cécile Henry Isabelle Corre Lucas Treps Nicolas Clere |
| author_facet | Clara Bourreau Emilie Navarro Marine Cotinat Morgane Krejbich François Guillonneau Catherine Guette Alice Boissard Cécile Henry Isabelle Corre Lucas Treps Nicolas Clere |
| author_sort | Clara Bourreau |
| collection | DOAJ |
| description | ABSTRACT Aim The tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial‐to‐mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer‐associated fibroblasts (CAFs). Our study aimed to investigate the consequences of exposure to different lung tumor secretomes on EC phenotype and plasticity. Materials and Methods Conditioned media (CM) were prepared from the tumor cell lines A549, H1755, H23, H1437, and H1975. Proliferation and migration of ECs treated with these CMs were assessed by Cyquant and Incucyte technologies, respectively. The angiogenic capacity of ECs was assessed by following tubulogenesis on Matrigel. Phenotypic changes in treated ECs were detected by flow cytometry. Morphological analysis of actin fibers was performed by immunohistochemistry, while proteomic analysis by mass spectrometry was used to identify the protein content of secretomes. Results A change of the endothelial phenotype was found when human umbilical vein endothelial cells (HUVECs) were treated with different CMs. This phenotypic change was associated with a morphological change, an increase in both stress fiber expression and spontaneous migration. Furthermore, an increase in mesenchymal markers (α‐SMA and CD44) confirmed the phenotypic changes. However, the secretomes did not modify the rate of double‐labeled cells (vWF+/α‐SMA+ or CD31+/CD44+). Proteomic analysis identified potential targets involved in the EndMT with therapeutic relevance. Conclusion Taken together, these data suggest that CMs can induce partial EndMT. |
| format | Article |
| id | doaj-art-18f05edb78c648f7b5385badf1b3ea3f |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-18f05edb78c648f7b5385badf1b3ea3f2025-08-20T02:59:07ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70707Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal TransitionClara Bourreau0Emilie Navarro1Marine Cotinat2Morgane Krejbich3François Guillonneau4Catherine Guette5Alice Boissard6Cécile Henry7Isabelle Corre8Lucas Treps9Nicolas Clere10Univ Angers, Inserm, CNRS, MINT, SFR ICAT Angers FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceInstitut de Cancérologie de l'Ouest Angers FranceInstitut de Cancérologie de l'Ouest Angers FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceNantes Université, Université d'Angers, CHU Nantes, Inserm, CNRS, CRCI2NA Nantes FranceUniv Angers, Inserm, CNRS, MINT, SFR ICAT Angers FranceABSTRACT Aim The tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial‐to‐mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer‐associated fibroblasts (CAFs). Our study aimed to investigate the consequences of exposure to different lung tumor secretomes on EC phenotype and plasticity. Materials and Methods Conditioned media (CM) were prepared from the tumor cell lines A549, H1755, H23, H1437, and H1975. Proliferation and migration of ECs treated with these CMs were assessed by Cyquant and Incucyte technologies, respectively. The angiogenic capacity of ECs was assessed by following tubulogenesis on Matrigel. Phenotypic changes in treated ECs were detected by flow cytometry. Morphological analysis of actin fibers was performed by immunohistochemistry, while proteomic analysis by mass spectrometry was used to identify the protein content of secretomes. Results A change of the endothelial phenotype was found when human umbilical vein endothelial cells (HUVECs) were treated with different CMs. This phenotypic change was associated with a morphological change, an increase in both stress fiber expression and spontaneous migration. Furthermore, an increase in mesenchymal markers (α‐SMA and CD44) confirmed the phenotypic changes. However, the secretomes did not modify the rate of double‐labeled cells (vWF+/α‐SMA+ or CD31+/CD44+). Proteomic analysis identified potential targets involved in the EndMT with therapeutic relevance. Conclusion Taken together, these data suggest that CMs can induce partial EndMT.https://doi.org/10.1002/cam4.70707EndMTendothelial cell plasticityendothelial‐to‐mesenchymal transitionnon‐small cell lung cancersecretome |
| spellingShingle | Clara Bourreau Emilie Navarro Marine Cotinat Morgane Krejbich François Guillonneau Catherine Guette Alice Boissard Cécile Henry Isabelle Corre Lucas Treps Nicolas Clere Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition Cancer Medicine EndMT endothelial cell plasticity endothelial‐to‐mesenchymal transition non‐small cell lung cancer secretome |
| title | Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition |
| title_full | Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition |
| title_fullStr | Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition |
| title_full_unstemmed | Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition |
| title_short | Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition |
| title_sort | secretomes from non small cell lung cancer cells induce endothelial plasticity through a partial endothelial to mesenchymal transition |
| topic | EndMT endothelial cell plasticity endothelial‐to‐mesenchymal transition non‐small cell lung cancer secretome |
| url | https://doi.org/10.1002/cam4.70707 |
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