Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas
Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time...
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MDPI AG
2020-10-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/11/865 |
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| author | Noemi Eiro Sandra Cid María Fraile Jorge Ruben Cabrera Luis O. Gonzalez Francisco J. Vizoso |
| author_facet | Noemi Eiro Sandra Cid María Fraile Jorge Ruben Cabrera Luis O. Gonzalez Francisco J. Vizoso |
| author_sort | Noemi Eiro |
| collection | DOAJ |
| description | Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes. |
| first_indexed | 2024-03-10T15:24:00Z |
| format | Article |
| id | doaj.art-bf454f7f49ea445aafcdca27bac19d2f |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T15:24:00Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-bf454f7f49ea445aafcdca27bac19d2f2023-11-20T18:16:53ZengMDPI AGDiagnostics2075-44182020-10-01101186510.3390/diagnostics10110865Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast CarcinomasNoemi Eiro0Sandra Cid1María Fraile2Jorge Ruben Cabrera3Luis O. Gonzalez4Francisco J. Vizoso5Unit Research, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainUnit Research, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainUnit Research, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainUnit Research, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainDepartment of Pathological Anatomy, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainUnit Research, Fundación Hospital de Jove, Gijón, 33290 Asturias, SpainLuminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes.https://www.mdpi.com/2075-4418/10/11/865cancer associated fibroblaststumor stromabreast cancerMMP11IGF2 |
| spellingShingle | Noemi Eiro Sandra Cid María Fraile Jorge Ruben Cabrera Luis O. Gonzalez Francisco J. Vizoso Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas Diagnostics cancer associated fibroblasts tumor stroma breast cancer MMP11 IGF2 |
| title | Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas |
| title_full | Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas |
| title_fullStr | Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas |
| title_full_unstemmed | Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas |
| title_short | Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas |
| title_sort | analysis of the gene expression profile of stromal pro tumor factors in cancer associated fibroblasts from luminal breast carcinomas |
| topic | cancer associated fibroblasts tumor stroma breast cancer MMP11 IGF2 |
| url | https://www.mdpi.com/2075-4418/10/11/865 |
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