title: Endosialin-Expressing Pericytes Promote Metastatic Dissemination.
abstract: Metastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts share a number of traits, including the upregulated expression of the transmembrane receptor endosialin (CD248). Comparative experiments in wild-type and endosialin-deficient mice revealed that stromal endosialin does not affect primary tumor growth but strongly promotes spontaneous metastasis. Mechanistically, endosialin-expressing pericytes in the primary tumor facilitate distant site metastasis by promoting tumor cell intravasation in a cell contact-dependent manner, resulting in elevated numbers of circulating tumor cells. Corresponding to these preclinical experiments, in independent cohorts of primary human breast cancers, upregulated endosialin expression significantly correlates with increased metastasis and poorer patient survival. Together, the data demonstrate a critical role for endosialin-expressing primary tumor pericytes in mediating metastatic dissemination and identify endosialin as a promising therapeutic target in breast cancer. Cancer Res; 76(18); 5313-25. ©2016 AACR.
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Carmen
authors.initials: C
authors.lastname: Viski
authors.affiliation: Division of Vascular Oncology and Metastasis (DKFZ-ZMBH Alliance), German Cancer Research Center, Heidelberg, Germany. Department of Vascular Biology and Tumor Angiogenesis (CBTM), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Courtney
authors.initials: C
authors.lastname: König
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kijewska
authors.affiliation: Division of Vascular Oncology and Metastasis (DKFZ-ZMBH Alliance), German Cancer Research Center, Heidelberg, Germany. Institute of Pathology, Heidelberg University, Heidelberg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom. clare.isacke@icr.ac.uk augustin@angiogenese.de.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
authors.affiliation: Division of Vascular Oncology and Metastasis (DKFZ-ZMBH Alliance), German Cancer Research Center, Heidelberg, Germany. Department of Vascular Biology and Tumor Angiogenesis (CBTM), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. German Cancer Consortium, Heidelberg, Germany. clare.isacke@icr.ac.uk augustin@angiogenese.de.
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D009363:Neoplasm Proteins; C509258:tumor endothelial marker 1, mouse