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CXCR4 and JUNB double-positive disseminated tumor cells are detected frequently in breast cancer patients at primary diagnosis

Kallergi Galatea, Hoffmann Oliver, Bittner Ann-Kathrin, Papadimitriou Lina, Katsarou Spyridoula D., Zacharopoulou Nefeli, Zervakis Michail, Sfakianakis Stelios, Stournaras Christos, Georgoulias Vassilis, Kimmig, Rainer, Kasimir-Bauer, Sabine, 1963-

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URIhttp://purl.tuc.gr/dl/dias/A9DFD49C-5659-4A36-94B9-E50787C717C4-
Identifierhttps://doi.org/10.1177/1758835919895754-
Identifierhttps://journals.sagepub.com/doi/full/10.1177/1758835919895754-
Languageen-
Extent12 pagesen
Extent769,01 kilobytesen
TitleCXCR4 and JUNB double-positive disseminated tumor cells are detected frequently in breast cancer patients at primary diagnosisen
CreatorKallergi Galateaen
CreatorHoffmann Oliveren
CreatorBittner Ann-Kathrinen
CreatorPapadimitriou Linaen
CreatorKatsarou Spyridoula D.en
CreatorZacharopoulou Nefelien
CreatorZervakis Michailen
CreatorΖερβακης Μιχαηλel
CreatorSfakianakis Steliosen
CreatorStournaras Christosen
CreatorGeorgoulias Vassilisen
CreatorKimmig, Raineren
CreatorKasimir-Bauer, Sabine, 1963-en
PublisherSAGE Publicationsen
Content SummaryBackground: The chemokine receptor CXCR4 and the transcription factor JUNB, expressed on a variety of tumor cells, seem to play an important role in the metastatic process. Since disseminated tumor cells (DTCs) in the bone marrow (BM) have been associated with worse outcomes, we evaluated the expression of CXCR4 and JUNB in DTCs of primary, nonmetastatic breast cancer (BC) patients before the onset of any systemic treatment. Methods: Bilateral BM (10 ml) aspirations of 39 hormone receptor (HR)-positive, HER2-negative BC patients were assessed for the presence of DTCs using the following combination of antibodies: pan-cytokeratin (A45-B/B3)/CXCR4/JUNB. An expression pattern of the examined proteins was created using confocal laser scanning microscopy, Image J software and BC cell lines. Results: CXCR4 was overexpressed in cancer cells and DTCs, with the following hierarchy of expression: SKBR3 > MCF7 > DTCs > MDA-MB231. Accordingly, the expression pattern of JUNB was: DTCs > MDA-MB231 > SKBR3 > MCF7. The mean intensity of CXCR4 (6411 ± 334) and JUNB (27725.64 ± 470) in DTCs was statistically higher compared with BM hematopoietic cells (2009 ± 456, p = 0.001; and 11112.89 ± 545, p = 0.001, respectively). The (CXCR4+JUNB+CK+) phenotype was the most frequently detected [90% (35/39)], followed by the (CXCR4–JUNB+CK+) phenotype [36% (14/39)]. However, (CXCR4+JUNB–CK+) tumor cells were found in only 5% (3/39) of patients. Those patients harboring DTCs with the (CXCR4+JUNB+CK+) phenotype revealed lower overall survival (Cox regression: p = 0.023). Conclusions: (CXCR4+JUNB+CK+)-expressing DTCs, detected frequently in the BM of BC patients, seem to identify a subgroup of patients at higher risk for relapse that may be considered for close follow up.en
Type of ItemPeer-Reviewed Journal Publicationen
Type of ItemΔημοσίευση σε Περιοδικό με Κριτέςel
Licensehttp://creativecommons.org/licenses/by-nc/4.0/en
Date of Item2021-09-07-
Date of Publication2020-
SubjectCXCR4en
SubjectDisseminated tumor cellsen
SubjectDormancyen
SubjectJUNBen
SubjectPrimary breast canceren
Bibliographic CitationG. Kallergi, O. Hoffmann, A.-K. Bittner, L. Papadimitriou, S. D. Katsarou, N. Zacharopoulou, M. Zervakis, S. Sfakianakis, C. Stournaras, V. Georgoulias, R. Kimmig, and S. Kasimir-Bauer, “CXCR4 and JUNB double-positive disseminated tumor cells are detected frequently in breast cancer patients at primary diagnosis,” Ther. Adv. Med. Oncol., vol. 12, Jan. 2020. doi: 10.1177/1758835919895754en

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