文章：

黏液蛋白在癌症中的作用：细胞表面的保护和控制

Mucins in cancer: protection and control of the cell surface

原文发布日期：2004-01-01

DOI: 10.1038/nrc1251

类型: Review Article

开放获取: 否

要点：

1. The outermost area of a typical aerodigestive epithelial surface consists of secreted gel-forming mucins, and serves as a point of interface with air, food, enzymes, acid pH, salt, bacteria and viruses. The secreted mucin layer might also contact the cell surface through interactions with membrane-associated mucins or other cell-surface molecules.
2. Complex mucin gels have been shown to capture and hold biologically active molecules that might function as indicators of molecular or physical breach of the mucin layer and, following their release, might incite inflammatory, repair or healing processes.
3. Cell-surface-associated mucins are bound to cells by an integral transmembrane domain and have relatively short cytoplasmic tails that associate with cytoskeletal elements, cytosolic adaptor proteins and/or participate in signal transduction. Mucins might serve as cell-surface receptors and sensors, and conduct signals in response to external stimuli that lead to coordinated cellular responses that include proliferation, differentiation, apoptosis or secretion of specialized cellular products.
4. Cancer cells, especially adenocarcinomas, express aberrant forms or amounts of mucins. The expression of distinct oligosaccharide structures, together with differential glycosylation of mucin core proteins, confers on tumour cells an enormous range of potential ligands for interaction with other receptors at the cell surface.
5. Cancer cells might use mucins in much the same way as normal epithelia — for protection from adverse growth conditions and to control the local molecular microenvironment during invasion and metastasis.
6. Mucins are hypothesized to contribute to tumour invasion by simultaneously disrupting existing interactions between opposing cells (anti-adhesion) and establishing new ligands for interaction between the invading cell and the adjoining cells (adhesion).
7. Mucins could contribute to the regulation of differentiation and proliferation of tumour cells, through ligand–receptor interactions (for example, between MUC4 and ERBB2 (also known as HER2/neu) and morphogenetic signal transduction.
8. Two of the most widely used serum diagnostic assays for adenocarcinomas (CA19-9 and CA125) recognize epitopes that are found on mucins. Several immunologically based clinical-therapy trials target mucins that are expressed by adenocarcinomas, including monoclonal-antibody-based therapies and tumour vaccines.

要点翻译：

1. 典型气道消化道上皮表面的最外层由分泌性凝胶形成粘蛋白构成，成为与空气、食物、酶、酸性pH环境、盐类、细菌及病毒相互作用的界面。分泌性粘蛋白层还可通过与膜结合粘蛋白或其他细胞表面分子的相互作用接触细胞表面。
2. 研究显示，复合粘蛋白凝胶能捕获并滞留具有生物活性的分子，这些分子可能作为粘蛋白层发生分子或物理性破坏的指示信号，并在释放后激发炎症、修复或愈合过程。
3. 细胞表面相关粘蛋白通过跨膜结构域锚定于细胞，其胞质尾段较短，可与细胞骨架元件、胞质衔接蛋白结合和/或参与信号转导。粘蛋白可作为细胞表面受体和传感器，响应外部刺激传导信号，从而引发包括增殖、分化、凋亡或特殊细胞产物分泌在内的协调细胞反应。
4. 癌细胞（尤其是腺癌）会表达异常形式或数量的粘蛋白。特定寡糖结构的表达与粘蛋白核心蛋白的差异化糖基化共同作用，使肿瘤细胞表面具备大量可与其它受体相互作用的潜在配体。
5. 癌细胞可能以与正常上皮细胞相似的方式利用粘蛋白——抵御不利生长条件，并在侵袭和转移过程中控制局部分子微环境。
6. 学界提出假说认为，粘蛋白通过同时破坏相邻细胞间的现有相互作用（抗粘附）并为侵袭细胞与邻近细胞间建立新配体连接（粘附）来促进肿瘤侵袭。
7. 粘蛋白可能通过配体-受体相互作用（如MUC4与ERBB2（亦称HER2/neu）之间的相互作用）及形态发生信号转导，参与调控肿瘤细胞的分化与增殖。
8. 目前腺癌最常用的两种血清诊断检测方法（CA19-9和CA125）所识别的表位均存在于粘蛋白上。多项基于免疫学的临床治疗试验以前腺癌表达的粘蛋白为靶点，包括单克隆抗体疗法和肿瘤疫苗。

英文摘要：

Paraneoplastic neurological degenerations (PNDs) are neurological disorders that develop in patients with cancer. PNDs are triggered by an effective antitumour immune response against neuronal antigens that are expressed in cancer cells, which subsequently develops into autoimmune neurodegenerative disease. Studying patients with PND has offered the opportunity to gain unique insights into mechanisms of tumour immunity and has provided the potential to apply this knowledge to patients with cancer in general.

摘要翻译： 

黏蛋白——一类被复杂寡糖高度糖基化的大型胞外蛋白——在上皮表面构建选择性分子屏障，并参与形态发生信号转导。其表达或糖基化的改变伴随癌症的发生，影响细胞生长、分化、转化、黏附、侵袭及免疫监视。黏蛋白已被用作癌症诊断标志物，并正被研究作为癌症治疗靶点。

原文链接：

Mucins in cancer: protection and control of the cell surface