Univ. Medical Center
The crosstalk between
metastatic cancer cells and target sites is critical for the development and
progression of metastases. Disruption of this interaction will allow to design
mechanism-based effective and specific therapeutic interventions for
We have established a co-culture
system of cells derived from different tumor entities and MG63 human
osteoblast-like cells to analyze tumor cell invasion. We could show that cancer cell invasion was
dramatically increased when cocultured with hOB or MG63. We use this in vitro model to examine the influence of various pharmaceuticals on migration and
invasion of the tumor cells on cellular as well as molecular level.
Using a real-time PCR
method based on detection of human-specific alu sequences measuring
accurately the amount of human tumor DNA in athymic mouse organs we
analyze metastasis formation in vivo.
(EMT) is a cellular development program characterized by loss of cell adhesion
and increased cell mobility. It is essential for numerous processes including metastasis. We have generated “aggressive”
MCF-7 breast cancer cells (MCF-7-EMT), which show significantly
increased invasion in contrast to wild type MCF-7 (MCF-7 WT) cells. In
addition, MCF-7-EMT cells differ in their
metastatic behavior in vivo and in expression of invasion and/or EMT relevant genes. With the breast cancer cell lines MCF-7-EMT and MCF-7 WT cells we have an
excellent model of cells for further studies of EMT and invasion in vitro and in vivo.
Role of S100A4, CYR61, RhoA, and RhoC signaling in EMT and metastasis of breast cancer.
Part I: Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 05/15/2006
for 3 years: Influence of GnRH analogs on bone-directed metastasis of breast cancer cells
in vitro and in vivo.
Part II: Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 04/17/2009
for 3 years: Effects of gene products of the metastasis-suppressor-gene KISS1 on proliferation,
metastasis and gene expression of breast cancers in vitro and in vivo.
- Part III: Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 09/16/2016
for 3 years: Signaling pathways of cell invasion as target for the therapy of metastatic breast cancer.
von Alten J, Fister
S, Schulz H, Viereck V, Frosch KH, Emons G, Gründker C (2006) GnRH analogs reduce
invasiveness of human breast cancer cells. Breast Cancer Research and Treatment
Schubert A, Schulz
H, Emons G, Gründker C (2008) Expression of OPG and RANKL in HCC70 breast cancer cells
and effects of GnRH treatment on RANKL expression. Gynecological
Olbrich T, Ziegler E, Türk G, Schubert A, Emons
G, Gründker C (2010) Kisspeptin-10 inhibits bone-directed migration of GPR54-positive
breast cancer cells: evidence for a dose-window effect. Gynecologic Oncology 119:571-578
Schubert A, Hawighorst
T, Emons G, Gründker C (2011) Agonist and antagonists of GnRH-I and -II reduce metastasis
of triple-negative human breast cancer cells in vivo. Breast Cancer Research
and Treatment 130(3):783-790
Ziegler E, Olbricht T, Emons G, Gründker
C (2013) Antiproliferative effects of kisspeptin-10 depend on
artificial GPR54 (KiSS1R) expression levels. Oncology Reports 29(2):549-554
Schmidt E, Haase M, Ziegler E,
Emons G, Gründker C (2014) Kisspeptin-10 inhibits stromal-derived factor-1-induced
invasion of human endometrial cancer cells. International Journal of Gynecological Cancer 24(2):210-217
- Ziegler E, Hansen M-T, Haase M, Emons G, Gründker C (2014) Generation of MCF-7 cells with aggressive metastatic potential in vitro and in vivo. Breast Cancer Research and Treatment 148(2):269-277
Gründker C, Bauerschmitz G,
Knapp J, Schmidt E, Olbrich T, Emons G (2015) Inhibition of SDF-1/CXCR4
system-induced epithelial-mesenchymal transition by kisspeptin-10. Breast Cancer Reseach and Treatment 152(1):41-50
C, Bauerschmitz G, Schubert A, Emons G (2016) Invasion and increased
expression of S100A4 and CYR61 in mesenchymal transformed breast cancer
cells is downregulated by GnRH. International Journal of Oncology 48(6):2713-2721
Gründker C, Emons G (2017) The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis. Frontiers in Endocrinology 8:187