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000119599 1001_ $$0P:(DE-HGF)0$$aBaccelli, Irène$$b0$$eFirst author
000119599 245__ $$aCo-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients.
000119599 260__ $$a[S.l.]$$bImpact Journals LLC$$c2014
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000119599 520__ $$aAlthough luminal-type primary breast cancer can be efficiently treated, development of metastatic disease remains a significant clinical problem. We have previously shown that luminal-type circulating tumor cells (CTCs) co-expressing the tyrosine-kinase MET and CD47, a ligand involved in cancer cell evasion from macrophage scavenging, are able to initiate metastasis in xenografts. Here, we investigated the clinical relevance of MET-CD47 co-expression in 255 hormone receptor positive breast tumors by immunohistochemistry and found a 10.3- year mean overall-survival difference between MET-CD47 double-positive and double-negative patients (p<0.001) MET-CD47 co-expression defined a novel independent prognosticator for overall-survival by multivariate analysis (Cox proportional hazards model: HR: 4.1, p<0.002) and CD47 expression alone or in combination with MET was strongly associated with lymph node metastasis. Furthermore, flow cytometric analysis of metastatic patient blood revealed consistent presence of MET+CD47+ CTCs (range 0.8 - 33.3% of CTCs) and their frequency was associated with increased metastatic spread. Finally, primary uncultured CTCs with high MET+CD47+ content showed an enhanced capacity to initiate metastasis in mice. Detection and targeting of MET and CD47 may thus provide a rational basis for risk stratification and treatment of patients with luminal-type breast cancer.
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000119599 650_7 $$2NLM Chemicals$$aAntigens, CD47
000119599 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000119599 650_7 $$2NLM Chemicals$$aCD47 protein, human
000119599 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aMET protein, human
000119599 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-met
000119599 7001_ $$aStenzinger, Albrecht$$b1
000119599 7001_ $$0P:(DE-He78)03fd0ab6ad061c771968971670c391e2$$aVogel, Vanessa$$b2$$udkfz
000119599 7001_ $$aPfitzner, Berit Maria$$b3
000119599 7001_ $$0P:(DE-He78)0812f68beb25392984d3abbe3c58b6d2$$aKlein, Corinna$$b4$$udkfz
000119599 7001_ $$aWallwiener, Markus$$b5
000119599 7001_ $$aScharpff, Martina$$b6
000119599 7001_ $$0P:(DE-HGF)0$$aSaini, Massimo$$b7
000119599 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b8$$udkfz
000119599 7001_ $$aSinn, Hans-Peter$$b9
000119599 7001_ $$0P:(DE-HGF)0$$aSchneeweiss, Andreas$$b10
000119599 7001_ $$0P:(DE-HGF)0$$aDenkert, Carsten$$b11
000119599 7001_ $$aWeichert, Wilko$$b12
000119599 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b13$$eLast author$$udkfz
000119599 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.2385$$gVol. 5, no. 18, p. 8147 - 8160$$n18$$p8147 - 8160$$tOncoTarget$$v5$$x1949-2553$$y2014
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