ADSCs and adipocytes are the main producers in the autotaxin-lysophosphatidic acid axis of breast cancer and healthy mammary tissue in vitro

Journal article


Publication Details

Author(s): Schmid R, Wolf K, Robering JW, Strauss S, Strissel P, Strick R, Rübner M, Fasching PA, Horch RE, Kremer A, Boos A, Weigand A
Journal: Bmc Cancer
Publication year: 2018
Volume: 18
Journal issue: 1
ISSN: 1471-2407


Abstract

BACKGROUND: Breast cancer is the most common malignancy in women affecting one out of eight females throughout their lives. Autotaxin (ATX) is upregulated in breast cancer which results in increased lysophosphatidic acid (LPA) formation within the tumor. This study's aim was to identify the role of different mammary cell populations within the ATX-LPA axis.
METHODS: Epithelial-cell-adhesion-molecule-positive (EpCAM) and -negative cells from breast tumors, adipose-derived stem cells (ADSCs) of tumor-adjacent and tumor-distant mammary fat were isolated and compared to healthy ADSCs, mammary epithelial cells (HMECs), and mesenchymal cells (MES) of healthy mammary tissue (n = 4 each) and further to well-established breast (cancer) cell lines.
RESULTS: mRNA expression analyses revealed that ADSCs and MES largely expressed LPA receptor 1 (LPAR1) while epithelial cells mainly expressed LPAR6. LPA 18:1 activated all the cell populations and cell lines by rise in cytosolic free calcium concentrations. MES and ADSCs expressed ATX whereas epithelial cells did not. ADSCs revealed the highest expression in ATX with a significant decline after adipogenic differentiation in healthy ADSCs, whereas ATX expression increased in ADSCs from tumor patients. Breast (cancer) cell lines did not express ATX. Transmigration of MES was stimulated by LPA whereas an inhibitory effect was observed in epithelial cells with no differences between tumors and healthy cells. Triple-negative breast cancer (TNBC) cell lines were also stimulated and the transmigration partly inhibited using the LPA receptor antagonist Ki16425.
CONCLUSIONS: We here show that each mammary cell population plays a different role in the ATX-LPA axis with ADSCs and adipocytes being the main source of ATX in tumor patients in our experimental setting. Inhibitors of this axis may therefore present a valuable target for pharmacological therapies.


FAU Authors / FAU Editors

Boos, Anja Dr.
Plastisch- und Handchirurgische Klinik
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Horch, Raymund E. Prof. Dr.
Professur für Plastische Chirurgie und Handchirurgie
Kremer, Andreas PD Dr.
Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
Robering, Jan Willem
Plastisch- und Handchirurgische Klinik
Rübner, Matthias Dr. rer. nat.
Frauenklinik
Schmid, Rafael
Lehrstuhl für Biochemie und Molekulare Medizin
Strick, Reiner Prof. Dr.
Medizinische Fakultät
Strissel, Pamela PD Dr.
Medizinische Fakultät
Kengelbach-Weigand, Annika Dr.
Plastisch- und Handchirurgische Klinik
Wolf, Katharina Dr. rer. nat.
Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie


How to cite

APA:
Schmid, R., Wolf, K., Robering, J.W., Strauss, S., Strissel, P., Strick, R.,... Weigand, A. (2018). ADSCs and adipocytes are the main producers in the autotaxin-lysophosphatidic acid axis of breast cancer and healthy mammary tissue in vitro. Bmc Cancer, 18(1). https://dx.doi.org/10.1186/s12885-018-5166-z

MLA:
Schmid, Rafael, et al. "ADSCs and adipocytes are the main producers in the autotaxin-lysophosphatidic acid axis of breast cancer and healthy mammary tissue in vitro." Bmc Cancer 18.1 (2018).

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Last updated on 2019-17-01 at 10:23