Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity.
Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity.
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DOI：
10.3892/mmr.2012.1189
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Tsuboi S
中科院分区：
文献类型：
--
作者：
Okamoto T;Yoneyama MS;Hatakeyama S;Mori K;Yamamoto H;Koie T;Saitoh H;Yamaya K;Funyu T;Fukuda M;Ohyama C;Tsuboi S
核心2 β-1，6-N-乙酰葡糖胺转移酶（C2 GnT）在细胞表面糖蛋白的O-聚糖（核心2 O-聚糖）中形成N-乙酰葡糖胺分支。我们以前发现，C2 GnT的表达与前列腺癌患者的预后不良呈正相关。然而，其预后不良的详细机制仍不清楚。在目前的研究中，我们报告说，核心2 O-聚糖所携带的表面MUC 1糖蛋白的前列腺癌细胞在逃避NK细胞免疫起着重要的作用。在表达C2 GnT的前列腺癌细胞中，MUC 1核心2 O-聚糖被聚-N-乙酰乳糖胺修饰。携带聚-N-乙酰乳糖胺的MUC 1糖蛋白减弱了癌细胞与NK细胞的相互作用，导致NK细胞分泌颗粒酶B减少。聚-N-乙酰乳糖胺也干扰肿瘤坏死因子相关凋亡诱导配体（TRAIL）进入癌细胞表面的能力。聚-N-乙酰乳糖胺对NK细胞的这些作用使得表达C2 GnT的前列腺癌细胞对NK细胞的细胞毒性具有抗性。相比之下，携带较少量聚-N-乙酰乳糖胺的C2 GnT缺陷型前列腺癌细胞比表达C2 GnT的前列腺癌细胞对NK细胞的细胞毒性显著更敏感。我们的研究结果强烈表明，表达C2 GnT的前列腺癌细胞逃避NK细胞免疫，并在宿主血液循环中存活更长时间，从而导致促进前列腺癌转移。
Core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N-acetylglucosamine branch in the O-glycans (core2 O-glycans) of cell surface glycoproteins. We previously revealed that the expression of C2GnT is positively correlated with poor prognosis in prostate cancer patients. However, the detailed mechanisms underlying their poor prognosis remain unclear. In the current study, we report that the core2 O-glycans carried by the surface MUC1 glycoproteins of prostate cancer cells play an important role in the evasion of NK cell immunity. In C2GnT-expressing prostate cancer cells, the MUC1 core2 O-glycans are modified with poly-N-acetyllactosamine. MUC1 glycoproteins carrying poly-N-acetyllactosamine attenuated the interaction of the cancer cells with NK cells, resulting in decreased secretion of granzyme B by the NK cells. Poly-N-acetyllactosamine also interfered with the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to access the cancer cell surface. These effects of poly-N-acetyllactosamine on NK cells render C2GnT-expressing prostate cancer cells resistant to NK cell cytotoxicity. By contrast, C2GnT-deficient prostate cancer cells carrying a lower amount of poly-N-acetyllactosamine than the C2GnT-expressing prostate cancer cells were significantly more susceptible to NK cell cytotoxicity. Our results strongly suggest that C2GnT-expressing prostate cancer cells evade NK cell immunity and survive longer in the host blood circulation, thereby resulting in the promotion of prostate cancer metastasis.
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影响因子：
254.7
作者：
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通讯作者：
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影响因子：
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Tsuboi S
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影响因子：
4.3
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