The role and regulation of tumour-associated hyaluronan.
The role and regulation of tumour-associated hyaluronan.
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肿瘤相关透明质酸的作用和调节。
DOI：
10.1002/9780470513774.ch10
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Toole,BP
中科院分区：
文献类型：
--
作者：
Knudson,W;Biswas,C;Li,XQ;Nemec,RE;Toole,BP
糖胺聚糖透明质酸水平的显着升高通常与人类和动物肿瘤有关。在兔 V2 癌中，肿瘤相关透明质酸水平升高也与侵袭性密切相关。因此，我们启动了研究，以更好地确定透明质酸合成在肿瘤组织中的作用和调节。在细胞培养中，许多肿瘤细胞类型合成透明质酸的能力降低，即使源自富含透明质酸的肿瘤。我们发现，其中一些相同的细胞仍然可以刺激正常成纤维细胞合成透明质酸。在 LX-1 人肺癌细胞系中，这种刺激潜力存在于膜结合的、热敏感的、亲脂性的细胞表面糖蛋白中。这些数据表明肿瘤相关透明质酸的产生是通过肿瘤-基质细胞相互作用发生的。我们最近证明，一些人类肿瘤细胞还具有未占据的、高亲和力的透明质酸细胞表面结合位点，这可能允许肿瘤细胞直接与富含透明质酸的细胞外基质相互作用。这种相互作用反过来可能允许肿瘤细胞使用透明质酸作为粘附和运动的支持。然后，透明质酸的空间组织可以引导肿瘤细胞进入周围的基质。我们尝试使用特异性识别透明质酸的形态学探针来可视化人类肿瘤组织冰冻切片内透明质酸原位的空间沉积。透明质酸最显着地出现在部分降解的结缔组织中。
Significantly increased levels of the glycosaminoglycan hyaluronan are often associated with human and animal tumours. In the rabbit V2 carcinoma elevated levels of tumour‐associated hyaluronan are also closely correlated with invasiveness. We have therefore initiated studies to better define the role and regulation of hyaluronan synthesis in tumour tissues. In cell culture many tumour cell types have reduced capacities to synthesize hyaluronan even when derived from tumours enriched in hyaluronan. We showed that several of these same cells can nevertheless stimulate hyaluronan synthesis by normal fibroblasts. In the LX‐1 human lung carcinoma cell line this stimulatory potential resides in a membrane‐bound, heat‐sensitive, lipophilic, cell surface glycoprotein. These data suggest that production of tumour‐associated hyaluronan occurs via tumour‐stromal cell interactions. We recently demonstrated that some human tumour cells also possess unoccupied, high affinity, cell surface binding sites for hyaluronan which may allow tumour cells to interact directly with hyaluronan‐enriched extracellular matrices. This interaction may in turn allow tumour cells to use hyaluronan as a support for adhesion and locomotion. The spatial organization of hyaluronan could then function to guide tumour cells into surrounding stroma. We attempted to visualize this spatial deposition of hyaluronanin situwithin frozen sections of human tumour tissue using a morphological probe that specifically recognizes hyaluronan. Hyaluronan appears most prominently in the partially degraded connective tissue.