Interaction between extracellular cancer matrix and stromal breast cells

Issue title: Selected post-conference papers of the 38th Conference of the German Society for Clinical Microcirculation and Hemorheology, 21-23 November 2019, Braunschweig, Germany

Guest editors: P. Wiggermann, A. Krüger-Genge and F. Jung

Article type: Research Article

Authors: Gehmert, Sanga^{a; b; *} | Lehoczky, Gyözö^{c; d} | Loibl, Markus^{b; e} | Jung, Friedrich^f | Prantl, Lukas^{b; g} | Gehmert, Sebastian^{b; c}

Affiliations: [a] Department of Gynecology and Obstetrics, Kantonsspital Baselland, Liestal, Switzerland | [b] Applied Stem Cell Research Center, University Medical Center Regensburg, Regensburg, Germany | [c] Department of Orthopedics, University Children’s Hospital Basel, Basel, Switzerland | [d] Department of Biomedicine, University Hospital Basel, Basel, Switzerland | [e] Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany | [f] Institute of Biotechnology, Brandenburg University of Technology, Senftenberg, Germany | [g] Department of Plastic and Hand Surgery, University Hospital Regensburg, Regensburg, Germany

Correspondence: [*] Corresponding author: Sanga Gehmert; Email: s.gehmert@gmail.com.

Abstract: INTRODUCTION:Stromal-epithelial interactions are fundamental for normal organ development and there is a multitude of evidence that the different components of the microenvironment are also necessary for the maintenance and promotion of the “tumor organ”. Deregulated tumor associated extracellular matrix (tECM) is a hallmark of cancer, causing an alteration in the amount and composition of the different components (i.e. proteins, proteoglycans, glycoproteins and polysaccharids) of the ECM. As epithelial-stromal interactions are reciprocal, it is possible that tECM itself is able to initiate tumor development. We therefore established a mouse model to examine the influence of tECM of murine breast cancer on developing breast tissue in mice. MATERIALS AND METHODS:Breast cancer was established in 5 BALB/c mice by subcutaneous injection of 1×106 4T1 cells in 100μl PBS into the left mammary fat pad. The mammary fat pad including the primary tumor was excised after two weeks, decellularised and labelled as tumor extracellular matrix (tECM). Tumor ECM of 4T1 tumors was implanted into the 4th inguinal mammary fat pad of BALB/c mice (n = 5) aged 5 days. After 12 weeks the fourth mammary fat pad including the primary tumor was excised. Tissue was used for paraffin embedding and mouse breast cancer PCR array. Murine breast cancer tissue (BCT) and normal murine breast tissue (BT) served as control. RESULTS:Gene array analysis of 84 breast cancer-specific transcripts revealed that the mammary gland cells which were exposed to tumor ECM (tECM-BT) showed a similarly high overexpression for 22 genes as apparent for breast cancer tissue (BCT). The corresponding scatter plot showed a high agreement in the expression of the examined genes between the mammary gland cells which were exposed to tumor ECM and the breast cancer tissue. DISCUSSION:Our results clearly demonstrate that the tECM is able to shift the gene expression pattern of murine mammary epithelial cells towards that of carcinoma, indicating a role in breast cancer initiation. These data underlines that the acellular component of the tumor (ECM) can lead to a transformation of mammary gland tissue cells. These data show for the first time that the interaction of normal breast tissue cells with tumor ECM leads to an exchange of information and a consecutive overexpression of tumor-specific genes.

Keywords: Breast cancer, extracellular matrix, microenvironment, epithelial-stromal interaction

DOI: 10.3233/CH-199234

Journal: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 45-52, 2020