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Cancer-associated fibroblasts affect breast cancer cell gene expression, invasion and angiogenesis

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Abstract

Purpose

It has been reported that stromal cell features may affect the clinical outcome of breast cancer patients. Cancer associated fibroblasts (CAFs) represent one of the most abundant cell types within the breast cancer stroma. Here, we aimed to explore the influence of CAFs on breast cancer gene expression, as well as on invasion and angiogenesis.

Methods

qRT-PCR was used to evaluate the expression of several cancer progression related genes (S100A4, TGFβ, FGF2, FGF7, PDGFA, PDGFB, VEGFA, IL-6, IL-8, uPA, MMP2, MMP9, MMP11 and TIMP1) in the human breast cancer-derived cell lines MCF-7 and MDA-MB-231, before and after co-culture with CAFs. Stromal mononuclear inflammatory cell (MIC) MMP11 expression was used to stratify primary tumors. In addition, we assessed the in vitro effects of CAFs on both MDA-MB-231 breast cancer cell invasion and endothelial cell (HUVEC) tube formation.

Results

We found that the expression levels of most of the genes tested were significantly increased in both breast cancer-derived cell lines after co-culture with CAFs from either MMP11+ or MMP11- MIC tumors. IL-6 and IL-8 showed an increased expression in both cancer-derived cell lines after co-culture with CAFs from MMP11+ MIC tumors. We also found that the invasive and angiogenic capacities of, respectively, MDA-MB-231 and HUVEC cells were increased after co-culture with CAFs, especially those from MMP11+ MIC tumors.

Conclusions

Our data indicate that tumor-derived CAFs can induce up-regulation of genes involved in breast cancer progression. Our data additionally indicate that CAFs, especially those derived from MMP11+ MIC tumors, can promote breast cancer cell invasion and angiogenesis.

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Acknowledgments

This work was supported by grants to F. V from the Instituto de Salud Carlos III (PI13/02745) and from the Consejería de Economía y Empleo del Principado de Asturias (GRUPIN14-116), and to R.P-F. from the Ministerio de Economia y Competividad (SAF2015-69221-R). A.M-O. is a predoctoral fellow from the Ministerio de Educación (FPU14/00548). S.C. was recipient of a predoctoral fellowship financed by the Gobierno del Principado de Asturias “Severo Ochoa” PhD Program (BP14-128).

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Author notes

  1. Noemi Eiro and Lucía González contributed equally to this work.

Authors and Affiliations

  1. Unidad de Investigación, Fundación Hospital de Jove, 33290, Gijón, Asturias, Spain

    Noemi Eiro, Lucía González, Belen Fernandez-Garcia, Luis O. González, Sandra Cid & Francisco J. Vizoso

  2. Department of Physiology-CIMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Anxo Martínez-Ordoñez & Román Perez-Fernandez

  3. Servicio de Anatomía Patológica, Fundación Hospital de Jove, 33290, Gijón, Asturias, Spain

    Luis O. González

  4. Servicio de Anatomía Patológica, Hospital de Cabueñes, 33394, Gijón, Asturias, Spain

    Francisco Dominguez

  5. Servicio de Cirugía General, Fundación Hospital de Jove, 33290, Gijón, Asturias, Spain

    Francisco J. Vizoso

Authors
  1. Noemi Eiro
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  2. Lucía González
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  5. Luis O. González
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  9. Francisco J. Vizoso
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Correspondence to Noemi Eiro or Francisco J. Vizoso.

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The study adheres to national regulations and was approved by our Institution’s Ethics and Investigation Committee.

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The authors have no conflicts of interests to disclose.

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Eiro, N., González, L., Martínez-Ordoñez, A. et al. Cancer-associated fibroblasts affect breast cancer cell gene expression, invasion and angiogenesis. Cell Oncol. 41, 369–378 (2018). https://doi.org/10.1007/s13402-018-0371-y

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