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Chemokine axes in breast cancer : factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Chemokine axes in breast cancer : factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

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WEITZENFELD, Polina, Olga KOSSOVER, Cindy KOERNER, Tsipi MESHEL, Stefan WIEMANN, Dror SELIKTAR, Daniel F. LEGLER, Adit BEN-BARUCH, 2016. Chemokine axes in breast cancer : factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors. In: Journal of Leukocyte Biology : JLB. 99(6), pp. 1009-1025. ISSN 0741-5400. eISSN 1938-3673

@article{Weitzenfeld2016-06-01Chemo-34807, title={Chemokine axes in breast cancer : factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors}, year={2016}, doi={10.1189/jlb.3MA0815-373R}, number={6}, volume={99}, issn={0741-5400}, journal={Journal of Leukocyte Biology : JLB}, pages={1009--1025}, author={Weitzenfeld, Polina and Kossover, Olga and Koerner, Cindy and Meshel, Tsipi and Wiemann, Stefan and Seliktar, Dror and Legler, Daniel F. and Ben-Baruch, Adit} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/34807"> <dc:contributor>Meshel, Tsipi</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-07-15T12:39:24Z</dcterms:available> <dc:contributor>Weitzenfeld, Polina</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-07-15T12:39:24Z</dc:date> <dc:creator>Ben-Baruch, Adit</dc:creator> <dc:contributor>Seliktar, Dror</dc:contributor> <dc:creator>Koerner, Cindy</dc:creator> <dc:contributor>Ben-Baruch, Adit</dc:contributor> <dcterms:title>Chemokine axes in breast cancer : factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors</dcterms:title> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/34807"/> <dc:creator>Wiemann, Stefan</dc:creator> <dcterms:abstract xml:lang="eng">Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype.</dcterms:abstract> <dc:creator>Meshel, Tsipi</dc:creator> <dcterms:issued>2016-06-01</dcterms:issued> <dc:contributor>Kossover, Olga</dc:contributor> <dc:contributor>Koerner, Cindy</dc:contributor> <dc:creator>Kossover, Olga</dc:creator> <dc:contributor>Wiemann, Stefan</dc:contributor> <dc:creator>Seliktar, Dror</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Legler, Daniel F.</dc:contributor> <dc:creator>Legler, Daniel F.</dc:creator> <dc:creator>Weitzenfeld, Polina</dc:creator> </rdf:Description> </rdf:RDF>

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