Endosialin-Expressing Pericytes Promote Metastatic Dissemination.
MetadataShow full item record
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.
Version of record
Mice, Inbred BALB C
Polymerase Chain Reaction
Molecular Cell Biology
License start date
Cancer Res, 2016, 76 (18), pp. 5313 - 5325
Showing items related by title, author, creator and subject.
Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma. Lee, JY; Garcia-Murillas, I; Cutts, RJ; De Castro, DG; Grove, L; Hurley, T; Wang, F; Nutting, C; Newbold, K; Harrington, K; Turner, N; Bhide, S (2017-09-05)BACKGROUND: Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for ...
Frentzas, S; Simoneau, E; Bridgeman, VL; Vermeulen, PB; Foo, S; Kostaras, E; Nathan, M; Wotherspoon, A; Gao, Z-H; Shi, Y; Van den Eynden, G; Daley, F; Peckitt, C; Tan, X; Salman, A; Lazaris, A; Gazinska, P; Berg, TJ; Eltahir, Z; Ritsma, L; Van Rheenen, J; Khashper, A; Brown, G; Nystrom, H; Sund, M; Van Laere, S; Loyer, E; Dirix, L; Cunningham, D; Metrakos, P; Reynolds, AR (2016-11)The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the ...
Yost, S; de Wolf, B; Hanks, S; Zachariou, A; Marcozzi, C; Clarke, M; de Voer, R; Etemad, B; Uijttewaal, E; Ramsay, E; Wylie, H; Elliott, A; Picton, S; Smith, A; Smithson, S; Seal, S; Ruark, E; Houge, G; Pines, J; Kops, GJPL; Rahman, N (2017-07)Through exome sequencing, we identified six individuals with biallelic loss-of-function mutations in TRIP13. All six developed Wilms tumor. Constitutional mosaic aneuploidies, microcephaly, developmental delay and seizures, ...