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Cellular Oncology
Published in: Cellular Oncology 4/2018

01-08-2018 | Original Paper

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

Authors: Noemi Eiro, Lucía González, Anxo Martínez-Ordoñez, Belen Fernandez-Garcia, Luis O. González, Sandra Cid, Francisco Dominguez, Román Perez-Fernandez, Francisco J. Vizoso

Published in: Cellular Oncology | Issue 4/2018

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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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Metadata
Title
Cancer-associated fibroblasts affect breast cancer cell gene expression, invasion and angiogenesis
Authors
Noemi Eiro
Lucía González
Anxo Martínez-Ordoñez
Belen Fernandez-Garcia
Luis O. González
Sandra Cid
Francisco Dominguez
Román Perez-Fernandez
Francisco J. Vizoso
Publication date
01-08-2018
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 4/2018
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-018-0371-y

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