Human sialidase as a cancer marker
Human sialidase as a cancer marker
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DOI：
10.1002/pmic.200800248
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发表时间：
2008-08-01
期刊：
影响因子：
3.4
通讯作者：
Fujiya, Tsuneaki
中科院分区：
文献类型：
--
作者：
Miyagi, Taeko;Wada, Tadashi;Fujiya, Tsuneaki
细胞表面糖蛋白和糖脂的唾液化改变与癌细胞的恶性表型密切相关，包括转移潜力和侵袭性。许多临床使用的癌症相关抗原在分子糖链的末端位置含有唾液酸。为了阐明其分子机制，我们重点研究了唾液酸酶，它能催化糖缀合物中唾液酸残基的去除。迄今为止鉴定的四种人类唾液酸酶在致癌过程中以不同的方式发挥作用。其中一种在溶酶体中发现的唾液酸酶在癌症中表现出下调，促进锚定独立生长和转移能力，而另一种在质膜中发现的唾液酸酶则表现出显著上调，导致细胞凋亡抑制。研究发现，通过实时荧光定量PCR检测唾液酸酶的mRNA水平，可以区分癌组织和非癌组织，甚至可以确定某些癌症的病理分期。利用抗质膜唾液酸酶抗体对癌组织进行免疫组化，有助于临床诊断。本文就唾液酸酶在肿瘤中的表达变化及其作为肿瘤标志物的临床应用前景作一综述。人唾液酸酶确实与恶性肿瘤有关，可能是癌症诊断和治疗的潜在靶点。
Altered sialylation of cell surface glycoproteins and glycolipids is closely related to the malignant phenotype of cancer cells, including the metastatic potential and invasiveness. Many cancer-related antigens in clinical use contain sialic acids at the terminal position of sugar chains in the molecules. To elucidate the molecular mechanism, we focused our investigation on sialidase, which catalyzes the removal of sialic acid residues from the glycoconjugates. Four types of human sialidases identified to date behave in different manners during carcinogenesis. One of the sialidases, found in the lysosomes, showed downregulation in cancers, promoting anchorage-independent growth, and metastatic ability, while another, found in the plasma membrane, showed marked upregulation, causing apoptosis suppression. It was found that estimation of the mRNA levels of sialidases by real-time PCR allowed discrimination of cancerous from noncancerous tissues and even determination of the pathological stage in some cancers. Immuno-histochemistry of cancer tissues using the antibody against the plasma membrane sialidase was useful for clinical diagnosis. This paper briefly summarizes our findings of the altered sialidase expression in cancers and the possibility of their clinical application as cancer markers. Human sialidases are indeed related to malignancy and may be potential targets for cancer diagnosis and therapy.