Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker
Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express p...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/7/560 |
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| author | Lesly Jazmin Bueno-Urquiza Marisol Godínez-Rubí Julio César Villegas-Pineda Alejandra Natali Vega-Magaña Luis Felipe Jave-Suárez Ana Graciela Puebla-Mora Gloria Estefanía Aguirre-Sandoval María Guadalupe Martínez-Silva Adrián Ramírez-de-Arellano Ana Laura Pereira-Suárez |
| author_facet | Lesly Jazmin Bueno-Urquiza Marisol Godínez-Rubí Julio César Villegas-Pineda Alejandra Natali Vega-Magaña Luis Felipe Jave-Suárez Ana Graciela Puebla-Mora Gloria Estefanía Aguirre-Sandoval María Guadalupe Martínez-Silva Adrián Ramírez-de-Arellano Ana Laura Pereira-Suárez |
| author_sort | Lesly Jazmin Bueno-Urquiza |
| collection | DOAJ |
| description | Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA− FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression. |
| first_indexed | 2024-04-24T10:47:26Z |
| format | Article |
| id | doaj.art-20f45027899d486092c023e749a7ea4d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T10:47:26Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-20f45027899d486092c023e749a7ea4d2024-04-12T13:16:23ZengMDPI AGCells2073-44092024-03-0113756010.3390/cells13070560Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation MarkerLesly Jazmin Bueno-Urquiza0Marisol Godínez-Rubí1Julio César Villegas-Pineda2Alejandra Natali Vega-Magaña3Luis Felipe Jave-Suárez4Ana Graciela Puebla-Mora5Gloria Estefanía Aguirre-Sandoval6María Guadalupe Martínez-Silva7Adrián Ramírez-de-Arellano8Ana Laura Pereira-Suárez9Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoInstituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDivisión de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, MexicoDepartamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Anatomía Patológica, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, MexicoInstituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoInstituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoCervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA− FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.https://www.mdpi.com/2073-4409/13/7/560cancer-associated fibroblastsfibroblast activation proteincervical cancermesenquimal stem cellsheterogeneous phenotypes |
| spellingShingle | Lesly Jazmin Bueno-Urquiza Marisol Godínez-Rubí Julio César Villegas-Pineda Alejandra Natali Vega-Magaña Luis Felipe Jave-Suárez Ana Graciela Puebla-Mora Gloria Estefanía Aguirre-Sandoval María Guadalupe Martínez-Silva Adrián Ramírez-de-Arellano Ana Laura Pereira-Suárez Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker Cells cancer-associated fibroblasts fibroblast activation protein cervical cancer mesenquimal stem cells heterogeneous phenotypes |
| title | Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker |
| title_full | Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker |
| title_fullStr | Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker |
| title_full_unstemmed | Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker |
| title_short | Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker |
| title_sort | phenotypic heterogeneity of cancer associated fibroblasts in cervical cancer progression fap as a central activation marker |
| topic | cancer-associated fibroblasts fibroblast activation protein cervical cancer mesenquimal stem cells heterogeneous phenotypes |
| url | https://www.mdpi.com/2073-4409/13/7/560 |
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