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01-01-2013 | Preclinical Study

Prospective dual role of mesenchymal stem cells in breast tumor microenvironment

Authors: Christiane Senst, Timo Nazari-Shafti, Stefan Kruger, Kirstin Höner Zu Bentrup, Charles L. Dupin, Abigail E. Chaffin, Sudesh K. Srivastav, Philipp M. Wörner, Asim B. Abdel-Mageed, Eckhard U. Alt, Reza Izadpanah

Published in: Breast Cancer Research and Treatment | Issue 1/2013

Abstract

Breast cancer tissue is a heterogeneous cellular milieu comprising cancer and host cells. The interaction between breast malignant and non-malignant cells takes place in breast tumor microenvironment (TM), and has a crucial role in breast cancer progression. In addition to cellular component of TM, it mainly consists of cytokines released by tumor cells. The tumor-tropic capacity of mesenchymal stem cells (MSCs) and their interaction with breast TM is an active area of investigation. In the present communication, the interplay between the breast resident adipose tissue-derived MSCs (B-ASCs) and breast TM was studied. It was found that a distinct subset of B-ASCs display a strong affinity for conditioned media (CM) from two breast cancer cell lines, MDA-MB 231 (MDA-CM) and MCF-7 (MCF-CM). The expressions of several cytokines including angiogenin, GM-CSF, IL-6, GRO-α and IL-8 in MDA-CM and MCF-CM have been identified. Upon functional analysis a crucial role for GRO-α and IL-8 in B-ASCs migration was detected. The B-ASC migration was found to be via negative regulation of RECK and enhanced expression of MMPs. Furthermore, transcriptome analysis showed that migratory subpopulation express both pro- and anti-tumorigenic genes and microRNAs (miRNA). Importantly, we observed that the migratory cells exhibit similar gene and miRNA attributes as those seen in B-ASCs of breast cancer patients. These findings are novel and suggest that in breast cancer, B-ASCs migrate to the proximity of tumor foci. Characterization of the molecular mechanisms involved in the interplay between B-ASCs and breast TM will help in understanding the probable role of B-ASCs in breast cancer development, and could pave way for anticancer therapies.

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Title: Prospective dual role of mesenchymal stem cells in breast tumor microenvironment
Authors: Christiane Senst
Timo Nazari-Shafti
Stefan Kruger
Kirstin Höner Zu Bentrup
Charles L. Dupin
Abigail E. Chaffin
Sudesh K. Srivastav
Philipp M. Wörner
Asim B. Abdel-Mageed
Eckhard U. Alt
Reza Izadpanah
Publication date: 01-01-2013
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2321-0

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