V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis
V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis
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DOI：
10.1038/labinvest.3700449
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发表时间：
2006-09-01
影响因子：
5
通讯作者：
Bassols, Anna
中科院分区：
文献类型：
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作者：
Miquel-Serra, Laia;Serra, Montserrat;Bassols, Anna
Versican是一种由几种肿瘤细胞类型产生的大型硫酸软骨素蛋白聚糖，包括恶性黑色素瘤，其以四种不同的剪接变体存在。细胞外基质中多功能蛋白聚糖的存在在肿瘤细胞生长、粘附和迁移中起作用，这可以通过改变多功能蛋白聚糖同种型之间的比例来改变。我们以前已经表明，在人黑色素瘤细胞系中多功能蛋白聚糖V3亚型的过表达显著降低了体外和体内细胞生长，因为V3过表达（LV3SN）培养的细胞以及由这些细胞产生的原发性肿瘤比它们的仅载体对应物（LXSN）生长得慢。在目前的工作中，我们已经扩展了这些观察结果，以证明延迟的细胞生长是由于多个事件，因为与LXSN相比，在LV3SN细胞和肿瘤中观察到增殖指数以及凋亡的差异。例如，LV3SN黑色素瘤细胞表现出响应EGF的MAPK的延迟激活，我们还进一步表征了源自裸鼠的V3转导的黑色素瘤细胞的原发性肿瘤，以确定其他事件是否影响V3肿瘤表型。例如，LV3SN肿瘤的透明质酸含量高于LXSN肿瘤，而其他相关基质成分和血管化不受影响。此外，裸鼠中的肺转移仅发生在携带LV3SN肿瘤的动物中，表明该分子具有双重作用，既作为肿瘤生长的抑制剂又作为转移诱导剂。
Versican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma, which exists as four different splice variants. The presence of versican in the extracellular matrix plays a role in tumor cell growth, adhesion and migration, which could be altered by altering the ratio between versican isoforms. We have previously shown that overexpression of the V3 isoform of versican in human melanoma cell lines markedly reduces cell growth in vitro and in vivo, since V3-overexpressing ( LV3SN) cultured cells as well as primary tumors arising from these cells grow slower than their vector-only counterparts ( LXSN). In the present work, we have extended these observations to demonstrate that the delayed cell growth is due to multiple events since differences in proliferative index as well as in apoptosis are observed in LV3SN cells and tumors compared to LXSN. For example, LV3SN melanoma cells exhibit delayed activation of MAPK in response to EGF, we have also characterized further the primary tumors originated in nude mice from V3-transduced melanoma cells to determine if other events affect the V3 tumor phenotype. For example, hyaluronan content of LV3SN tumors was higher than in LXSN tumors, whereas other related matrix components and vascularization were unaffected. Furthermore, lung metastasis in nude mice occurred only in animals carrying LV3SN tumors, indicating a dual role for this molecule, both as an inhibitor of tumor growth and a metastasis inductor.