دورية أكاديمية
Clinical importance of high-mannose, fucosylated, and complex N-glycans in breast cancer metastasis.
| العنوان: | Clinical importance of high-mannose, fucosylated, and complex N-glycans in breast cancer metastasis. |
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| المؤلفون: | Ščupáková K; Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands., Adelaja OT; The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research., Balluff B; Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands., Ayyappan V; The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research., Tressler CM; The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research., Jenkinson NM; The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research., Claes BS; Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands., Bowman AP; Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands., Cimino-Mathews AM; Department of Pathology.; The Sidney Kimmel Comprehensive Cancer Center, and., White MJ; Department of Pathology., Argani P; Department of Pathology.; The Sidney Kimmel Comprehensive Cancer Center, and., Heeren RM; Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands., Glunde K; The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.; The Sidney Kimmel Comprehensive Cancer Center, and.; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. |
| المصدر: | JCI insight [JCI Insight] 2021 Dec 22; Vol. 6 (24). Date of Electronic Publication: 2021 Dec 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Breast Neoplasms/*genetics , Mannose/*metabolism , Polysaccharides/*metabolism, Adult ; Aged ; Breast Neoplasms/pathology ; Female ; Glycosylation ; Humans ; Middle Aged ; Neoplasm Metastasis |
| مستخلص: | Background: Although aberrant glycosylation is recognized as a hallmark of cancer, glycosylation in clinical breast cancer (BC) metastasis has not yet been studied. While preclinical studies show that the glycocalyx coating of cancer cells is involved in adhesion, migration, and metastasis, glycosylation changes from primary tumor (PT) to various metastatic sites remain unknown in patients. Methods: We investigated N-glycosylation profiles in 17 metastatic BC patients from our rapid autopsy program. Primary breast tumor, lymph node metastases, multiple systemic metastases, and various normal tissue cores from each patient were arranged on unique single-patient tissue microarrays (TMAs). We performed mass spectrometry imaging (MSI) combined with extensive pathology annotation of these TMAs, and this process enabled spatially differentiated cell-based analysis of N-glycosylation patterns in metastatic BC. Results: N-glycan abundance increased during metastatic progression independently of BC subtype and treatment regimen, with high-mannose glycans most frequently elevated in BC metastases, followed by fucosylated and complex glycans. Bone metastasis, however, displayed increased core-fucosylation and decreased high-mannose glycans. Consistently, N-glycosylated proteins and N-glycan biosynthesis genes were differentially expressed during metastatic BC progression, with reduced expression of mannose-trimming enzymes and with elevated EpCAM, N-glycan branching, and sialyation enzymes in BC metastases versus PT. Conclusion: We show in patients that N-glycosylation of breast cancer cells undergoing metastasis occurs in a metastatic site-specific manner, supporting the clinical importance of high-mannose, fucosylated, and complex N-glycans as future diagnostic markers and therapeutic targets in metastatic BC. Funding: NIH grants R01CA213428, R01CA213492, R01CA264901, T32CA193145, Dutch Province Limburg "LINK", European Union ERA-NET TRANSCAN2-643638. |
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| معلومات مُعتمدة: | R01 CA213428 United States CA NCI NIH HHS; R01 CA213492 United States CA NCI NIH HHS; T32 CA193145 United States CA NCI NIH HHS; T32 GM136577 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Breast cancer; Glycobiology; Molecular pathology; Oncology |
| المشرفين على المادة: | 0 (Polysaccharides) PHA4727WTP (Mannose) |
| تواريخ الأحداث: | Date Created: 20211109 Date Completed: 20220308 Latest Revision: 20221115 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8783675 |
| DOI: | 10.1172/jci.insight.146945 |
| PMID: | 34752419 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.146945 |