Versican V1 isoform regulates cell-associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells.
Versican V1 isoform regulates cell-associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells.
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Versican V1 异构体在 Swarm 大鼠软骨肉瘤细胞中调节细胞相关基质形成和细胞行为，与聚集蛋白聚糖不同。
DOI：
10.1002/ijc.26230
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Ishiguro N.
中科院分区：
文献类型：
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作者：
Wasa J;Nishida Y;Shinomura T;Isogai Z;Futamura N;Urakawa H;Arai E;Kozawa E;Tsukushi S;Ishiguro N.
Versican是一种结合透明质酸的大型硫酸软骨素蛋白聚糖，由大型细胞外基质聚集体组成，已显示与肿瘤进展相关。没有研究检查多功能蛋白聚糖在软骨肉瘤中的作用，也没有将其与聚集蛋白聚糖进行比较。在临床标本中的人类软骨瘤，多功能蛋白聚糖的表达显着增加，在恶性肿瘤，而且，随着肿瘤分级的增加。为了阐明多功能蛋白聚糖在软骨肉瘤中的作用，使用Trap-In System将多功能蛋白聚糖剪接变体1、变体3或仅GFP稳定转染到Swarm大鼠软骨肉瘤细胞中。与V3-、GFP-转染或RCS细胞相比，Swarm大鼠软骨肉瘤细胞中多功能蛋白聚糖V1亚型的强制表达诱导细胞相关基质显著增加。Versican以类似于透明质酸的方式免疫定位，并且比聚集蛋白聚糖更扩散。锚依赖性和非依赖性生长不受多功能蛋白聚糖亚型表达的影响，而V1亚型转染显著增强了细胞运动性和迁移性。V1转染细胞在体内形成的肿瘤表现出更多的粘液瘤面积，并包括更多的梭形细胞。这些结果支持多功能蛋白聚糖比聚集蛋白聚糖具有形成更广泛的细胞相关基质的能力的概念，并且突出的基质形成更积极地改变软骨肉瘤的细胞行为。这些观察结果表明，多功能蛋白聚糖的表达可能作为软骨肉瘤的肿瘤分级确定的标志物，并可能有助于决定在更高级别的软骨肉瘤的治疗目标。
Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased. To clarify the roles of versican in chondrosarcoma, versican splicing variant 1, variant 3 or only GFP was stably transfected to Swarm rat chondrosarcoma cells with Trap‐In System. Forced expression of versican V1 isoform in Swarm rat chondrosarcoma cells induced a marked increase of cell‐associated matrix compared to V3‐, GFP‐ transfected or RCS cells. Versican was immunolocalized in a fashion similar to that of hyaluronan and more diffusively than aggrecan. Anchor‐dependent and ‐independent growth was not affected by versican isoform expression, whereas cell motility and migration were significantly enhanced by V1 isoform transfection. Tumors formedin vivowith V1‐transfected cells exhibited more myxomatous area and included more spindle shaped cells. These results support the concept that versican has the capacity to form more extensive cell‐associated matrix than aggrecan, and the prominent matrix formation alters the cell behavior of chondrosarcoma more aggressively. These observations suggest that versican expression may serve as a marker of tumor grade determination in chondrosarcoma and possibly help to decide on therapeutic targets in higher grades of chondrosarcoma.