Mac-2 binding protein is a novel E-selectin ligand expressed by breast cancer cells.
Mac-2 binding protein is a novel E-selectin ligand expressed by breast cancer cells.
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DOI：
10.1371/journal.pone.0044529
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Burdick MM
中科院分区：
文献类型：
--
作者：
Shirure VS;Reynolds NM;Burdick MM
血行转移涉及循环肿瘤细胞粘附到继发部位的血管内皮。我们假设乳腺癌细胞粘附是由内皮E-选择素与乳腺癌细胞上表达的糖蛋白反受体相互作用介导的。在平行板流动室粘附测定中测试时，在血行壁剪切速率下，ZR-75-1乳腺癌细胞特异性粘附于表达E-选择素的人脐静脉内皮细胞。与其E-选择素配体活性一致，ZR-75-1细胞表达HECA-452 mAb的流式细胞术可检测表位，其识别以唾液酸岩藻糖基化部分为代表的高效E-选择素配体。ZR-75-1细胞表达的多种E-选择素反应蛋白通过与E-选择素嵌合体（E-Ig嵌合体）的免疫沉淀和随后的Western印迹来显示。质谱分析的72 kDa的蛋白质，其中表现出最突出的E-选择素配体活性，对应于Mac-2结合蛋白（Mac-2BP），一个迄今未确定的E-选择素配体。免疫沉淀的Mac-2BP表达唾液酸岩藻糖基化的表位，并具有E-选择素配体活性，经HECA-452 mAb和E-Ig嵌合体Western blot检测，表明Mac-2BP是一种新型高效的E-选择素配体。此外，通过shRNA沉默来自ZR-75-1细胞的Mac-2BP的表达显著降低了它们在生理流动条件下与表达E-选择素的细胞的粘附，证实了Mac-2BP对完整细胞的功能性E-选择素配体活性。除ZR-75-1细胞外，其他几种E-选择素配体阳性乳腺癌细胞系表达Mac-2BP，通过Western blot和流式细胞术检测，表明Mac-2BP可能是多种乳腺癌类型中的E-选择素配体。此外，浸润性乳腺癌组织显示共定位的Mac-2BP和HECA-452抗原的表达，荧光显微镜，强调Mac-2BP作为E-选择素配体的可能作用。总之，乳腺癌细胞表达Mac-2BP作为一种新的E-选择素配体，潜在地揭示了乳腺癌的新的预后和治疗靶点。
Hematogenous metastasis involves the adhesion of circulating tumor cells to vascular endothelium of the secondary site. We hypothesized that breast cancer cell adhesion is mediated by interaction of endothelial E-selectin with its glycoprotein counter-receptor(s) expressed on breast cancer cells. At a hematogenous wall shear rate, ZR-75-1 breast cancer cells specifically adhered to E-selectin expressing human umbilical vein endothelial cells when tested in parallel plate flow chamber adhesion assays. Consistent with their E-selectin ligand activity, ZR-75-1 cells expressed flow cytometrically detectable epitopes of HECA-452 mAb, which recognizes high efficiency E-selectin ligands typified by sialofucosylated moieties. Multiple E-selectin reactive proteins expressed by ZR-75-1 cells were revealed by immunoprecipitation with E-selectin chimera (E-Ig chimera) followed by Western blotting. Mass spectrometry analysis of the 72 kDa protein, which exhibited the most prominent E-selectin ligand activity, corresponded to Mac-2 binding protein (Mac-2BP), a heretofore unidentified E-selectin ligand. Immunoprecipitated Mac-2BP expressed sialofucosylated epitopes and possessed E-selectin ligand activity when tested by Western blot analysis using HECA-452 mAb and E-Ig chimera, respectively, demonstrating that Mac-2BP is a novel high efficiency E-selectin ligand. Furthermore, silencing the expression of Mac-2BP from ZR-75-1 cells by shRNA markedly reduced their adhesion to E-selectin expressing cells under physiological flow conditions, confirming the functional E-selectin ligand activity of Mac-2BP on intact cells. In addition to ZR-75-1 cells, several other E-selectin ligand positive breast cancer cell lines expressed Mac-2BP as detected by Western blot and flow cytometry, suggesting that Mac-2BP may be an E-selectin ligand in a variety of breast cancer types. Further, invasive breast carcinoma tissue showed co-localized expression of Mac-2BP and HECA-452 antigens by fluorescence microscopy, underscoring the possible role of Mac-2BP as an E-selectin ligand. In summary, breast cancer cells express Mac-2BP as a novel E-selectin ligand, potentially revealing a new prognostic and therapeutic target for breast cancer.
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影响因子：
4.8
作者：
Chen, Shih-Hsun;Dallas, Matthew R.;Konstantopoulos, Konstantinos
通讯作者：
Konstantopoulos, Konstantinos
影响因子：
11.2
作者：
Dimitroff, CJ;Lechpammer, M;Kutok, JL
通讯作者：
Kutok, JL
影响因子：
3
作者：
Grassadonia, A;Tinari, N;Iacobelli, S
通讯作者：
Iacobelli, S
DOI：
10.1007/978-1-4419-7877-6_32
发表时间：
2011-01-01
期刊：
MOLECULAR IMMUNOLOGY OF COMPLEX CARBOHYDRATES-3
影响因子：
--
作者：
Konstantopoulos, Konstantinos;Thomas, Susan N.
通讯作者：
Thomas, Susan N.
影响因子：
3.5
作者：
IACOBELLI, S;BUCCI, I;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J