Show simple item record Bottai G Raschioni C Székely, Borbála Di Tommaso L Szász, Attila Marcell Losurdo A Győrffy, Balázs Ács, Balázs Torrisi R Karachaliou N Tőkés, Tímea Caruso M Kulka, Janina Roncalli M Santoro A Mantovani A Rosell R Reis-Filho JS Santarpia L 2018-06-25T07:30:33Z 2018-06-25T07:30:33Z 2016
dc.identifier.citation pagination=16033, pages: 10; journalVolume=2; journalTitle=NPJ BREAST CANCER;
dc.identifier.uri doi:10.1038/npjbcancer.2016.33
dc.description.abstract A subgroup of triple-negative breast cancer (TNBC) shows epithelial-to-mesenchymal transition (EMT) features, which are sustained by the interaction between cancer cells and tumor-associated macrophages (TAMs). In this study, the clinical relevance of 30 EMT-related kinases and the potential cross-talk with TAMs were investigated in a cohort of 203 TNBC patients treated with adjuvant chemotherapy. The prognostic value of the evaluated markers was validated in two independent cohorts of TNBC patients treated with adjuvant chemotherapy (N=95; N=137). In vitro, we investigated the potential synergism between cancer cells and TAMs. We found that the EMT-related kinase AXL showed the highest correlation with the frequency of CD163-positive macrophages (rS=0.503; P<0.0001). Relapsing TNBC patients presented high expression of AXL (P<0.0001) and CD163 (P<0.018), but only AXL retained independent prognostic significance in multivariate analysis (relapse-free survival, P=0.002; overall survival P=0.001). In vitro analysis demonstrated that AXL-expressing TNBC cells were able to polarize human macrophages towards an M2-like phenotype, and modulate a specific pattern of pro-tumor cytokines and chemokines. Selective AXL inhibition impaired the activity of M2-like macrophages, reducing cancer cell invasiveness, and restoring the sensitivity of breast cancer cells to chemotherapeutic drugs. These data suggest that the EMT-related kinase AXL overexpressed in cancer cells has prognostic significance, and contributes to the functional skewing of macrophage functions in TNBC. AXL inhibition may represent a novel strategy to target cancer cells, as well as tumor-promoting TAMs in TNBC.
dc.relation.ispartof urn:issn:2374-4677
dc.title AXL-associated tumor inflammation as a poor prognostic signature in chemotherapy-treated triple-negative breast cancer patients
dc.type Journal Article 2018-03-13T13:42:35Z
dc.language.rfc3066 en
dc.identifier.mtmt 3284318
dc.identifier.wos 000411077700001
dc.identifier.pubmed 28721387
dc.contributor.department SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika
dc.contributor.department SE/AOK/I/II. Sz. Patológiai Intézet
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote COI The authors declare no conflict of interest.

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