Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion.
Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion.
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DOI：
10.1007/s00109-009-0446-3
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发表时间：
2009-05
影响因子：
4.7
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Conrad, Fraser;Zhu, Xiaodong;Zhang, Xin;Chalkley, Robert J.;Burlingame, Alma L.;Marks, James D.;Liu, Bin
关键词：
从激素敏感型向激素不敏感型转移肿瘤的转变是前列腺癌治疗的主要挑战。在这一转变过程中差异表达的肿瘤抗原可能在赋予前列腺癌细胞在激素缺乏的环境中生长和转移到远端部位(如骨骼)的能力方面发挥重要作用，因此可能是治疗干预的靶点。为了确定伴随这种转变的那些分子，特别是细胞表面抗原，我们使用基于抗体库的亲和蛋白质组学方法，研究了激素敏感型前列腺癌LNCaP及其激素不敏感衍生物C4-2B之间细胞表面抗原谱的变化。我们选择了一个天然噬菌体抗体库来鉴定与C4-2B特异结合但不与LNCaP结合的人单链抗体。利用质谱仪，我们鉴定了其中一个抗体靶向抗原为ICAM-1/CD54/人鼻病毒受体。由该单链抗体产生的重组IgG1与ICAM-1的中和表位结合，并在体外通过细胞外基质阻断C4-2B细胞的侵袭。因此，ICAM-1在激素敏感的前列腺癌细胞系LNCaP向激素不敏感的衍生物C4-2B的转变过程中存在差异表达，在赋予C4-2B细胞侵袭能力方面发挥重要作用，因此可能成为治疗干预的靶点。
Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell surface antigens that accompany this transition, we studied the changes in cell surface antigenic profiles between a hormone-sensitive prostate cancer line LNCaP and its hormone-refractory derivative C4-2B, using an antibody library-based affinity proteomic approach. We selected a naïve phage antibody display library to identify human single-chain antibodies that bind specifically to C4-2B but not LNCaP. Using mass spectrometry, we identified one of the antibody-targeted antigens as the ICAM-1/CD54/human rhinovirus receptor. Recombinant IgG1 derived from this single-chain antibody binds to a neutralizing epitope of ICAM-1 and blocks C4-2B cell invasion through extracellular matrix in vitro. ICAM-1 is thus differentially expressed during the transition of the hormone-sensitive prostate cancer cell line LNCaP to its hormone-refractory derivative C4-2B, plays an important role in imparting the C4-2B line with the ability to invade, and may therefore be a target for therapeutic intervention.
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DOI：
10.1073/pnas.95.11.6157
发表时间：
1998-05-26
影响因子：
11.1
作者：
Sheets, MD;Amersdorfer, P;Marks, JD
通讯作者：
Marks, JD
影响因子：
7
作者：
Bidlingmaier, S;Liu, B
通讯作者：
Liu, B
影响因子：
11.2
作者：
Dimitroff, CJ;Lechpammer, M;Kutok, JL
通讯作者：
Kutok, JL
DOI：
10.1165/ajrcmb.19.3.3179
发表时间：
1998-09-01
影响因子：
6.4
作者：
Burke-Gaffney, A;Hellewell, PG
通讯作者：
Hellewell, PG
影响因子：
7
作者：
Bidlingmaier, Scott;Liu, Bin
通讯作者：
Liu, Bin