SULFs in human neoplasia: implication as progression and prognosis factors.
SULFs in human neoplasia: implication as progression and prognosis factors.
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DOI：
10.1186/1479-5876-9-72
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发表时间：
2011-05-21
影响因子：
7.4
通讯作者：
Klein B
中科院分区：
文献类型：
--
作者：
Bret C;Moreaux J;Schved JF;Hose D;Klein B
硫酸乙酰肝素链的硫酸化模式影响位于细胞表面的硫酸乙酰肝素蛋白聚糖介导的信号传导事件。SULF 1和SULF 2是两种能够切割乙酰肝素链内特异性6-O硫酸酯基团的内切硫酸酯酶。它们的作用可以调节信号传导过程，其中许多与癌症的发展和扩展具有关键相关性。SULF 1与各种癌症模型中的肿瘤抑制作用有关，而SULF 2失调与促肿瘤作用有关。然而，其他观察结果认为这些硫酸酯酶在癌症中的作用相互矛盾，表明它们在肿瘤微环境中的作用复杂。我们使用公开可用的基因表达数据，包括从新诊断的多发性骨髓瘤患者的两个队列、Oncomine癌症微阵列数据库、Amazonia数据库和ITTACA数据库获得的数据，将编码SULF 1、SULF 2和硫酸乙酰肝素蛋白聚糖的基因在一大组癌症样本中的表达与其正常组织对应物进行比较。我们还分析了与这些数据库相关的预后数据。我们在两个独立的大型患者队列中证实了原发性多发性骨髓瘤细胞中SULF 2的表达与预后不良相关。当与传统的多发性骨髓瘤预后因素一起考虑时，它仍然是一个独立的预测因子。此外，我们观察到SULF 2基因在皮肤癌、结直肠癌、睾丸畸胎瘤和肝癌中的过度表达。我们发现SULF 2在高级别葡萄膜黑色素瘤中显著过表达，与低级别相比，在结肠直肠癌患者中显著过表达，与良性结肠腺瘤相比。我们观察到，除了以前的观察，SULF 1基因的表达增加，T淋巴细胞白血病，急性髓细胞白血病和肾癌相比，相应的正常组织。此外，我们发现SULF 1高表达与肺腺癌预后不良相关。最后，SULF 1和SULF 2在6种癌症类型中同时过表达：脑癌、乳腺癌、头颈癌、肾癌、皮肤癌和睾丸癌。SULF 1和SULF 2在各种人类癌症类型中过表达，并可能与进展和预后相关。靶向SULF 1和/或SULF 2可能是开发新型癌症疗法的有趣策略。
The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within the heparan chains. Their action can modulate signaling processes, many of which with key relevance for cancer development and expansion. SULF1 has been associated with tumor suppressor effects in various models of cancer, whereas SULF2 dysregulation was in relation with protumorigenic actions. However, other observations argue for contradictory effects of these sulfatases in cancer, suggesting the complexity of their action in the tumor microenvironment. We compared the expression of the genes encoding SULF1, SULF2 and heparan sulfate proteoglycans in a large panel of cancer samples to their normal tissue counterparts using publicly available gene expression data, including the data obtained from two cohorts of newly-diagnosed multiple myeloma patients, the Oncomine Cancer Microarray database, the Amazonia data base and the ITTACA database. We also analysed prognosis data in relation with these databases. We demonstrated that SULF2 expression in primary multiple myeloma cells was associated with a poor prognosis in two independent large cohorts of patients. It remained an independent predictor when considered together with conventional multiple myeloma prognosis factors. Besides, we observed an over-representation of SULF2 gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that SULF2 was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma. We observed that, in addition to previous observations, SULF1 gene expression was increased in T prolymphocytic leukemia, acute myeloid leukemia and in renal carcinoma compared to corresponding normal tissues. Furthermore, we found that high SULF1 expression was associated with a poor prognosis in lung adenocarcinoma. Finally, SULF1 and SULF2 were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers. SULF1 and SULF2 are overexpressed in various human cancer types and can be associated to progression and prognosis. Targeting SULF1 and/or SULF2 could be interesting strategies to develop novel cancer therapies.
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影响因子：
45.3
作者：
Decaux, Olivier;Lode, Laurence;Minvielle, Stephane
通讯作者：
Minvielle, Stephane
影响因子：
25.7
作者：
Lai JP;Sandhu DS;Moser CD;Cazanave SC;Oseini AM;Shire AM;Shridhar V;Sanderson SO;Roberts LR
通讯作者：
Roberts LR
影响因子：
11.2
作者：
Chau, B. Nelson;Diaz, Robert L.;Cleary, Michele A.
通讯作者：
Cleary, Michele A.
影响因子：
4.8
作者：
Dai, YM;Yang, Y;Sanderson, RD
通讯作者：
Sanderson, RD
影响因子：
13.5
作者：
Lai, Jin-Ping;Sandhu, Dalbir S.;Roberts, Lewis R.
通讯作者：
Roberts, Lewis R.