Characterization of human breast cancer cells affected by coculture conditions and kisspeptin-10

Ziegler, Elke

dc.contributor.advisor	Gründker, Carsten Prof. Dr.	de
dc.contributor.author	Ziegler, Elke	de
dc.date.accessioned	2013-07-04T10:56:53Z	de
dc.date.available	2013-07-04T10:56:53Z	de
dc.date.issued	2013-07-04	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0001-BAA6-8	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3909
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Characterization of human breast cancer cells affected by coculture conditions and kisspeptin-10	de
dc.type	doctoralThesis	de
dc.contributor.referee	Gründker, Carsten Prof. Dr.	de
dc.date.examination	2013-06-18	de
dc.description.abstracteng	Breast cancer is the most common type of cancer in women. Lethality is mainly attributed to a severe metastatic spread in patients. Research in new therapeutic treatments demands the understanding of the metastatic processes and the interaction of tumor cells with the distant organ microenvironment. Therefore, a coculture cell system was studied on relations between human breast cancer cells and osteoblast-like osteosarcoma cells mimicking an important metastasis environment in bone. Kisspeptin-10, a peptide derived from the metastasis suppressor gene KISS1, interferes within this cell system by inhibition of invasion. An in fluence of kisspeptin-10 in vivo was further investigated to evaluate its eff ect as a possible therapeutic option in the metastatic breast cancer disease. Human breast cancer cells were classi ed by morphology, motility marker expression and their individual invasiveness. In coculture, epithelial-like cells showed a dramatic increase in invasion. Microarray gene analysis revealed potential factors of cell motility processes and immune response mechanisms, which were regulated by the interaction of breast cancer cells and osteosarcoma cells. An involvement of EMT was shown partially by upregulation of mesenchymal gene markers without an altered epithelial marker expression. CXCL12 was identifi ed as one important factor in invasive progression: the coculture e ffect may trigger invasion by an autocrine CXCL12/CXCR4 loop. Factors as EGF and interferons are possible new targets of investigations on the interaction of breast cancer cells and osteosarcoma cells. Kisspeptin-10 was studied in breast cancer xenografts for an infl uence on metastatic spread and tumor growth. Treatment with the peptide inhibited tumor growth. But investigations on cell proliferation in vitro revealed no antiproliferative eft ect. The role of kisspeptin-10 in angiogenetic processes is an interesting option as possible mechanism leading to decreased tumor size in treated animals. A conclusion could not be o ffered on an antimetastatic e ffect of kisspeptin-10 as possible therapeutic option in breast cancer based on the poor metastasis model in mice.	de
dc.contributor.coReferee	Dobbelstein, Matthias Prof. Dr.	de
dc.subject.eng	breast cancer	de
dc.subject.eng	metastasis	de
dc.subject.eng	coculture	de
dc.subject.eng	KISS1	de
dc.subject.eng	kisspeptin-10	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BAA6-8-4	de
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Gynäkologie / Geburtshilfe / Perinatologie - Allgemein- und Gesamtdarstellungen (PPN619876050)	de
dc.identifier.ppn	751154520	de

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Human- und Zahnmedizin [2877]

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