Clinical importance of high-mannose, fucosylated, and complex N-glycans in breast cancer metastasis.
Clinical importance of high-mannose, fucosylated, and complex N-glycans in breast cancer metastasis.
复制标题
DOI：
10.1172/jci.insight.146945
复制
发表时间：
2021-12-22
期刊：
影响因子：
8
通讯作者：
Glunde K
中科院分区：
文献类型：
--
作者：
Ščupáková K;Adelaja OT;Balluff B;Ayyappan V;Tressler CM;Jenkinson NM;Claes BS;Bowman AP;Cimino-Mathews AM;White MJ;Argani P;Heeren RM;Glunde K
背景虽然异常糖基化被认为是癌症的标志，但临床乳腺癌（BC）转移中的糖基化尚未研究。虽然临床前研究表明癌细胞的糖萼涂层参与粘附、迁移和转移，但患者中从原发性肿瘤（PT）到各种转移部位的糖基化变化仍然未知。方法.我们调查了17例转移性BC患者的N-糖基化谱，从我们的快速尸检程序。原发性乳腺肿瘤，淋巴结转移，多系统转移，和各种正常组织核心从每个病人都安排在独特的单一患者组织微阵列（TMA）。我们进行了质谱成像（MSI）结合这些TMA的广泛病理学注释，这一过程使转移性BC的N-糖基化模式的空间分化细胞为基础的分析。结果转移进展期间N-聚糖丰度增加，与BC亚型和治疗方案无关，高甘露糖聚糖在BC转移中最常升高，其次是岩藻糖基化和复合聚糖。然而，骨转移显示核心岩藻糖基化增加和高甘露糖聚糖减少。一致地，N-糖基化蛋白和N-聚糖生物合成基因在转移性BC进展期间差异表达，与PT相比，BC转移中甘露糖修剪酶的表达降低，EpCAM、N-聚糖分支和唾液酸化酶升高。结论我们在患者中发现，经历转移的乳腺癌细胞的N-糖基化以转移位点特异性的方式发生，支持高甘露糖、岩藻糖基化和复杂N-聚糖作为转移性BC的未来诊断标志物和治疗靶点的临床重要性。经费NIH赠款R 01 CA 213428、R 01 CA 213492、R 01 CA 264901、T32 CA 193145，荷兰省林布尔格“LINK”，欧盟ERA-NET TRANSCAN 2 -643638。
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.
登录
查看更多内容
DOI：
10.1083/jcb.139.5.1337
发表时间：
1997-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Litvinov SV;Balzar M;Winter MJ;Bakker HA;Briaire-de Bruijn IH;Prins F;Fleuren GJ;Warnaar SO
通讯作者：
Warnaar SO
影响因子：
7.4
作者：
Bowman, Andrew P.;Blakney, Greg T.;Smith, Donald F.
通讯作者：
Smith, Donald F.
影响因子：
3.8
作者：
Harrell, J. Chuck;Prat, Aleix;Perou, Charles M.
通讯作者：
Perou, Charles M.
影响因子：
2.6
作者：
Hay SB;Ferchen K;Chetal K;Grimes HL;Salomonis N
通讯作者：
Salomonis N
影响因子：
50.3
作者：
Li CW;Lim SO;Chung EM;Kim YS;Park AH;Yao J;Cha JH;Xia W;Chan LC;Kim T;Chang SS;Lee HH;Chou CK;Liu YL;Yeh HC;Perillo EP;Dunn AK;Kuo CW;Khoo KH;Hsu JL;Wu Y;Hsu JM;Yamaguchi H;Huang TH;Sahin AA;Hortobagyi GN;Yoo SS;Hung MC
通讯作者：
Hung MC