Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://www.sciencedirect.com/science/article/pii/S1570963920301722?via%3Dihub https://repositorio.unifesp.br/handle/11600/60497 https://doi.org/10.1016/j.bbapap.2020.140525 |
Resumo: | The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the phenotype of tumoral cells and have significant implications in cancer development and progression. In this study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators. The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the conditioned medium derived from ‘primed’ stromal cells (melanoma-stimulated fibroblasts) was more effective in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from nonstimulated fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment and enable tumoral cells to succeed in the process of melanoma progression and metastasis. Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression and metastasis. |
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Pessotti, Dayelle [UNIFESP]Andrade-Silva, Débora - Instituto ButantanSerrano, Solange - Instituto ButantanZelanis, André [UNIFESP]http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4778207Z42021-03-16T11:36:18Z2021-03-16T11:36:18Z2020-08-29https://www.sciencedirect.com/science/article/pii/S1570963920301722?via%3Dihub1570-9639https://repositorio.unifesp.br/handle/11600/60497https://doi.org/10.1016/j.bbapap.2020.140525The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the phenotype of tumoral cells and have significant implications in cancer development and progression. In this study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators. The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the conditioned medium derived from ‘primed’ stromal cells (melanoma-stimulated fibroblasts) was more effective in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from nonstimulated fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment and enable tumoral cells to succeed in the process of melanoma progression and metastasis. Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression and metastasis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)2014/06579-3, 2013/07467-1, 2016/16935-7, 2019/07282-8140525engUlrich BrandtBiochimica et Biophysica Acta (BBA) - Proteins and Proteomicsheterotypic signalingmelanomafibroblastCancer-associated fibroblastsphenotypic plasticityHeterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article186812info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPInstituto de Ciência e Tecnologia (ICT)Ciência e TecnologiaNão se aplicaORIGINALPessotti et al 2020.pdfPessotti et al 2020.pdfArtigo publicadoapplication/pdf4092952${dspace.ui.url}/bitstream/11600/60497/1/Pessotti%20et%20al%202020.pdfb0b7fdd226d011d7d6cecf74313e59b4MD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-85506${dspace.ui.url}/bitstream/11600/60497/2/license.txt43263b1849a89c412b6fdcb4cb65f60bMD52open accessTEXTPessotti et al 2020.pdf.txtPessotti et al 2020.pdf.txtExtracted texttext/plain48240${dspace.ui.url}/bitstream/11600/60497/9/Pessotti%20et%20al%202020.pdf.txt70653950822e55fbfe9fede4158de16cMD59open accessTHUMBNAILPessotti et al 2020.pdf.jpgPessotti et al 2020.pdf.jpgIM Thumbnailimage/jpeg6953${dspace.ui.url}/bitstream/11600/60497/11/Pessotti%20et%20al%202020.pdf.jpgd82c259b09657903099e907cf193a7acMD511open access11600/604972023-06-05 19:07:18.563open 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dm8gcmVmZXJlbnRlIMOgIE9icmEgZGV2ZSBpbmRpY2FyIGEgbGljZW7Dp2EgYXBsaWPDoXZlbCBlbSBjb250ZcO6ZG8gbGVnw612ZWwgcG9yIHNlcmVzIGh1bWFub3MgZSwgc2UgcG9zc8OtdmVsLCB0YW1iw6ltIGVtIG1ldGFkYWRvcyBsZWfDrXZlaXMgcG9yIG3DoXF1aW5hLiBBIGluZGljYcOnw6NvIGRhIGxpY2Vuw6dhIGFwbGljw6F2ZWwgZGV2ZSBzZXIgYWNvbXBhbmhhZGEgZGUgdW0gbGluayBwYXJhIG9zIHRlcm1vcyBkZSBsaWNlbmNpYW1lbnRvIG91IHN1YSBjw7NwaWEgaW50ZWdyYWwuCgo3LiBBdGVzdGEgcXVlIGEgT2JyYSBzdWJtZXRpZGEgbsOjbyBjb250w6ltIHF1YWxxdWVyIGluZm9ybWHDp8OjbyBjb25maWRlbmNpYWwgc3VhIG91IGRlIHRlcmNlaXJvcy4KCjguIENvbmNlZGUgw6AgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZGUgU8OjbyBQYXVsbyAoVU5JRkVTUCkgbyBkaXJlaXRvIG7Do28gZXhjbHVzaXZvIGRlIHJlYWxpemFyIHF1YWlzcXVlciBhbHRlcmHDp8O1ZXMgbmEgbcOtZGlhIG91IG5vIGZvcm1hdG8gZG8gYXJxdWl2byBwYXJhIHByb3DDs3NpdG9zIGRlIHByZXNlcnZhw6fDo28gZGlnaXRhbCwgZGUgYWNlc3NpYmlsaWRhZGUgZSBkZSBtZWxob3IgaWRlbnRpZmljYcOnw6NvIGRvIHRyYWJhbGhvIHN1Ym1ldGlkby4KCkFvIGNvbmNsdWlyIGFzIGV0YXBhcyBkbyBwcm9jZXNzbyBkZSBzdWJtaXNzw6NvIGRlIGFycXVpdm9zIG5vIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIFVOSUZFU1AsIGF0ZXN0byBxdWUgbGkgZSBjb25jb3JkZWkgaW50ZWdyYWxtZW50ZSBjb20gb3MgdGVybW9zIGFjaW1hIGRlbGltaXRhZG9zLCBzZW0gZmF6ZXIgcXVhbHF1ZXIgcmVzZXJ2YSBlIG5vdmFtZW50ZSBjb25maXJtYW5kbyBxdWUgY3VtcHJvIG9zIHJlcXVpc2l0b3MgaW5kaWNhZG9zIG5vIGl0ZW5zIG1lbmNpb25hZG9zIGFudGVyaW9ybWVudGUuCgpIYXZlbmRvIHF1YWxxdWVyIGRpc2NvcmTDom5jaWEgZW0gcmVsYcOnw6NvIGFvcyBwcmVzZW50ZXMgdGVybW9zIG91IG7Do28gc2UgdmVyaWZpY2FuZG8gbyBleGlnaWRvIG5vcyBpdGVucyBhbnRlcmlvcmVzLCB2b2PDqiBkZXZlIGludGVycm9tcGVyIGltZWRpYXRhbWVudGUgbyBwcm9jZXNzbyBkZSBzdWJtaXNzw6NvLiBBIGNvbnRpbnVpZGFkZSBkbyBwcm9jZXNzbyBlcXVpdmFsZSDDoCBjb25jb3Jkw6JuY2lhIGUgw6AgYXNzaW5hdHVyYSBkZXN0ZSBkb2N1bWVudG8sIGNvbSB0b2RhcyBhcyBjb25zZXF1w6puY2lhcyBuZWxlIHByZXZpc3Rhcywgc3VqZWl0YW5kby1zZSBvIHNpZ25hdMOhcmlvIGEgc2Fuw6fDtWVzIGNpdmlzIGUgY3JpbWluYWlzIGNhc28gbsOjbyBzZWphIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhdHJpbW9uaWFpcyBlL291IGNvbmV4b3MgYXBsaWPDoXZlaXMgw6AgT2JyYSBkZXBvc2l0YWRhIGR1cmFudGUgZXN0ZSBwcm9jZXNzbywgb3UgY2FzbyBuw6NvIHRlbmhhIG9idGlkbyBwcsOpdmlhIGUgZXhwcmVzc2EgYXV0b3JpemHDp8OjbyBkbyB0aXR1bGFyIHBhcmEgbyBkZXDDs3NpdG8gZSB0b2RvcyBvcyB1c29zIGRhIE9icmEgZW52b2x2aWRvcy4KClBhcmEgYSBzb2x1w6fDo28gZGUgcXVhbHF1ZXIgZMO6dmlkYSBxdWFudG8gYW9zIHRlcm1vcyBkZSBsaWNlbmNpYW1lbnRvIGUgcXVhbnRvIGFvIHByb2Nlc3NvIGRlIHN1Ym1pc3PDo28sIGVudmllIHVtYSBtZW5zYWdlbSBwYXJhIG8gZW5kZXJlw6dvIGRlIGUtbWFpbDogcmVwb3NpdG9yaW9AdW5pZmVzcC5ici4KClPDo28gUGF1bG8sIFRodSBNYXIgMTEgMTU6NDY6NTEgQlJUIDIwMjEuCg==Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:07:18Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.pt_BR.fl_str_mv |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
title |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
spellingShingle |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells Pessotti, Dayelle [UNIFESP] heterotypic signaling melanoma fibroblast Cancer-associated fibroblasts phenotypic plasticity |
title_short |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
title_full |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
title_fullStr |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
title_full_unstemmed |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
title_sort |
Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells |
author |
Pessotti, Dayelle [UNIFESP] |
author_facet |
Pessotti, Dayelle [UNIFESP] Andrade-Silva, Débora - Instituto Butantan Serrano, Solange - Instituto Butantan Zelanis, André [UNIFESP] |
author_role |
author |
author2 |
Andrade-Silva, Débora - Instituto Butantan Serrano, Solange - Instituto Butantan Zelanis, André [UNIFESP] |
author2_role |
author author author |
dc.contributor.authorLattes.pt_BR.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4778207Z4 |
dc.contributor.author.fl_str_mv |
Pessotti, Dayelle [UNIFESP] Andrade-Silva, Débora - Instituto Butantan Serrano, Solange - Instituto Butantan Zelanis, André [UNIFESP] |
dc.subject.por.fl_str_mv |
heterotypic signaling melanoma fibroblast Cancer-associated fibroblasts phenotypic plasticity |
topic |
heterotypic signaling melanoma fibroblast Cancer-associated fibroblasts phenotypic plasticity |
description |
The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the phenotype of tumoral cells and have significant implications in cancer development and progression. In this study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators. The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the conditioned medium derived from ‘primed’ stromal cells (melanoma-stimulated fibroblasts) was more effective in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from nonstimulated fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment and enable tumoral cells to succeed in the process of melanoma progression and metastasis. Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression and metastasis. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-08-29 |
dc.date.accessioned.fl_str_mv |
2021-03-16T11:36:18Z |
dc.date.available.fl_str_mv |
2021-03-16T11:36:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.pt_BR.fl_str_mv |
https://www.sciencedirect.com/science/article/pii/S1570963920301722?via%3Dihub |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/60497 |
dc.identifier.issn.pt_BR.fl_str_mv |
1570-9639 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1016/j.bbapap.2020.140525 |
url |
https://www.sciencedirect.com/science/article/pii/S1570963920301722?via%3Dihub https://repositorio.unifesp.br/handle/11600/60497 https://doi.org/10.1016/j.bbapap.2020.140525 |
identifier_str_mv |
1570-9639 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
140525 |
dc.publisher.none.fl_str_mv |
Ulrich Brandt |
publisher.none.fl_str_mv |
Ulrich Brandt |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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