دورية أكاديمية

CXCR4 mediates leukemic cell migration and survival in the testicular microenvironment.

التفاصيل البيبلوغرافية
العنوان: CXCR4 mediates leukemic cell migration and survival in the testicular microenvironment.
المؤلفون: Skroblyn T; Department of Microenvironmental Regulation in Autoimmunity and Cancer, Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany.; Department of Pediatric Oncology, Charité-University Medicine, Campus Virchow Klinikum, Berlin, Germany., Joedicke JJ; Department of Translational Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany., Pfau M; Department of Pediatric Oncology, Charité-University Medicine, Campus Virchow Klinikum, Berlin, Germany., Krüger K; Department of Microenvironmental Regulation in Autoimmunity and Cancer, Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany., Bourquin JP; Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland., Izraeli S; Schneider Children's Medical Center of Israel, Petach Tiqva, Israel.; Tel Aviv University, Tel Aviv, Israel., Eckert C; Department of Pediatric Oncology, Charité-University Medicine, Campus Virchow Klinikum, Berlin, Germany.; German Cancer Consortium, and German Cancer Research Center, Heidelberg, Germany., Höpken UE; Department of Microenvironmental Regulation in Autoimmunity and Cancer, Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany.
المصدر: The Journal of pathology [J Pathol] 2022 Sep; Vol. 258 (1), pp. 12-25. Date of Electronic Publication: 2022 Jun 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: John Wiley And Sons Country of Publication: England NLM ID: 0204634 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9896 (Electronic) Linking ISSN: 00223417 NLM ISO Abbreviation: J Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: Chichester : John Wiley And Sons
Original Publication: London, Oliver & Boyd.
مواضيع طبية MeSH: Precursor Cell Lymphoblastic Leukemia-Lymphoma*/pathology , Testis*/chemistry , Testis*/metabolism , Testis*/pathology, Animals ; Cell Movement ; Chemokine CXCL12/metabolism ; Child ; Humans ; Male ; Mice ; Receptors, CXCR4/metabolism ; Recurrence ; Signal Transduction ; Tumor Microenvironment
مستخلص: The testis is the second most frequent extramedullary site of relapse in pediatric acute lymphoblastic leukemia (ALL). The mechanism for B-cell (B) ALL cell migration towards and survival within the testis remains elusive. Here, we identified CXCL12-CXCR4 as the leading signaling axis for B-ALL cell migration and survival in the testicular leukemic niche. We combined analysis of primary human ALL with a novel patient-derived xenograft (PDX)-ALL mouse model with testicular involvement. Prerequisites for leukemic cell infiltration in the testis were prepubertal age of the recipient mice, high surface expression of CXCR4 on PDX-ALL cells, and CXCL12 secretion from the testicular stroma. Analysis of primary pediatric patient samples revealed that CXCR4 was the only chemokine receptor being robustly expressed on B-ALL cells both at the time of diagnosis and relapse. In affected patient testes, leukemic cells localized within the interstitial space in close proximity to testicular macrophages. Mouse macrophages isolated from affected testes, in the PDX model, revealed a macrophage polarization towards a M2-like phenotype in the presence of ALL cells. Therapeutically, blockade of CXCR4-mediated functions using an anti-CXCR4 antibody treatment completely abolished testicular infiltration of PDX-ALL cells and strongly impaired the overall development of leukemia. Collectively, we identified a prepubertal condition together with high CXCR4 expression as factors affecting the leukemia permissive testicular microenvironment. We propose CXCR4 as a promising target for therapeutic prevention of testicular relapses in childhood B-ALL. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
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فهرسة مساهمة: Keywords: B cell acute lymphoblastic leukemia; chemokine receptor CXCR4; macrophages; testis relapse; tumor microenvironment
المشرفين على المادة: 0 (CXCR4 protein, human)
0 (Chemokine CXCL12)
0 (Receptors, CXCR4)
تواريخ الأحداث: Date Created: 20220506 Date Completed: 20220815 Latest Revision: 20221019
رمز التحديث: 20231215
DOI: 10.1002/path.5924
PMID: 35522562
قاعدة البيانات: MEDLINE
الوصف
تدمد:1096-9896
DOI:10.1002/path.5924