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.
Frentzas, S; Simoneau, E; Bridgeman, VL; Vermeulen, PB; Foo, S; Kostaras, E; Nathan, M; Wotherspoon, A; Gao, ZH; 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 ...
Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. Crosby, T; Hurt, CN; Falk, S; Gollins, S; Staffurth, J; Ray, R; Bridgewater, JA; Geh, JI; Cunningham, D; Blazeby, J; Roy, R; Maughan, T; Griffiths, G; Mukherjee, S (2017-03-14)BACKGROUND: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and ...
Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance). Ellis, MJ; Suman, VJ; Hoog, J; Goncalves, R; Sanati, S; Creighton, CJ; DeSchryver, K; Crouch, E; Brink, A; Watson, M; Luo, J; Tao, Y; Barnes, M; Dowsett, M; Budd, GT; Winer, E; Silverman, P; Esserman, L; Carey, L; Ma, CX; Unzeitig, G; Pluard, T; Whitworth, P; Babiera, G; Guenther, JM; Dayao, Z; Ota, D; Leitch, M; Olson, JA; Allred, DC; Hunt, K (2017-04-01)Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 ...