Mitochondrial/cell-surface protein p32/gC1qR as a molecular target in tumor cells and tumor stroma.
Mitochondrial/cell-surface protein p32/gC1qR as a molecular target in tumor cells and tumor stroma.
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DOI：
10.1158/0008-5472.can-07-6752
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发表时间：
2008-09-01
期刊：
影响因子：
11.2
通讯作者：
Ruoslahti E
中科院分区：
文献类型：
--
作者：
Fogal V;Zhang L;Krajewski S;Ruoslahti E
肿瘤归巢肽LyP-1在某些肿瘤中选择性结合肿瘤相关淋巴管和肿瘤细胞，并表现出抗肿瘤作用。在这里，我们发现被称为p32或gC 1 qR的蛋白质是LyP-1的受体。各种人肿瘤细胞系在培养物中对p32表达呈阳性，并且在从阳性细胞系生长的异种移植肿瘤中表达增加。用抗p32抗体进行的流式细胞仪分析表明，p32阳性细胞系在细胞表面表达p32。这些细胞与LyP-1肽的结合和内化与细胞表面表达水平成比例，这与恶性程度相关，而不是与细胞中总的p32表达相关。与LyP-1肽一样，p32抗体突出显示了肿瘤中的缺氧区域，在那里它们与肿瘤细胞和表达巨噬细胞/髓样细胞标志物的细胞结合，并且经常出现在肿瘤细胞壁中。p32在人类肿瘤中的表达普遍存在，并且与相应的正常组织相比，p32水平通常大大升高。这些结果确立了p32，特别是其细胞表面表达形式，作为肿瘤细胞和肿瘤相关巨噬细胞/髓样细胞在缺氧/代谢剥夺区域的新标志物。p32在肿瘤中的独特定位和相对的肿瘤特异性使其成为肿瘤诊断和治疗的有用靶点。
A tumor homing peptide, LyP-1, selectively binds to tumor-associated lymphatic vessels and tumor cells in certain tumors and exhibits an anti-tumor effect. Here, we show that the protein known as p32 or gC1qR is the receptor for LyP-1. Various human tumor cell lines were positive for p32 expression in culture, and the expression was increased in xenograft tumors grown from the positive cell lines. FACS analyses with anti-p32 antibodies showed that p32-positive cell lines expressed p32 at the cell surface. These cells bound and internalized LyP-1 peptide in proportion to the cell surface expression level, which correlated with malignancy rather than total p32 expression in the cells. Like the LyP-1 peptide, p32 antibodies highlighted hypoxic areas in tumors, where they bound to both tumor cells and cells that expressed macrophage/myeloid cell markers and often appeared incorporated into the walls of tumor lymphatics. Significant p32 expression was common in human cancers and the p32 levels were often greatly elevated compared to the corresponding normal tissue. These results establish p32, particularly its cell surface-expressed form, as a new marker of tumor cells and tumor-associated macrophages/myeloid cells in hypoxic/metabolically deprived areas of tumors. Its unique localization in tumors and its relative tumor specificity may make p32 a useful target in tumor diagnosis and therapy.