Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis.
Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis.
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DOI：
10.1038/s41598-017-17613-6
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发表时间：
2017-12-08
影响因子：
4.6
通讯作者：
Hirohata S
中科院分区：
文献类型：
--
作者：
Asano K;Nelson CM;Nandadasa S;Aramaki-Hattori N;Lindner DJ;Alban T;Inagaki J;Ohtsuki T;Oohashi T;Apte SS;Hirohata S
葡聚糖蛋白与几种癌症的生长和转移有关。在这里，我们研究了间质蓖麻素对肿瘤生长和血管生成的潜在贡献。我们最初在几种癌细胞系中测定了versican的表达。其中，MDA-MB231和B16F10与Lewis肺癌（LLC）相比无或极低表达。值得注意的是，由这些细胞系产生的肿瘤比细胞系本身具有更高的versican水平，这表明宿主来源的肿瘤基质有贡献。在llc源性肿瘤中，肿瘤和间质均高水平表达versican。因此，肿瘤间质对肿瘤细胞质含量有重要贡献。Versican优先定位于肿瘤血管和肿瘤巨噬细胞附近。然而，ADAMTS蛋白酶产生的versican片段独特地定位于血管内皮。为了明确宿主/基质来源的小versican的影响，我们比较了产生小versican的B16F10细胞在Vcan hdf/+小鼠和野生型幼鼠中的肿瘤生长情况。Vcan hdf/+小鼠的肿瘤生长减少，毛细血管密度降低，肿瘤周围毛细血管积聚。这些发现说明了肿瘤细胞系表达的多变性，并证明了多变性一直是由基质组织贡献的，在基质组织中，它有助于肿瘤血管生成。
The proteoglycan versican is implicated in growth and metastases of several cancers. Here we investigated a potential contribution of stromal versican to tumor growth and angiogenesis. We initially determined versican expression by several cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal expression in contrast to Lewis lung carcinoma (LLC). Notably, tumors arising from these cell lines had higher versican levels than the cell lines themselves suggesting a contribution from the host-derived tumor stroma. In LLC-derived tumors, both the tumor and stroma expressed versican at high levels. Thus, tumor stroma can make a significant contribution to tumor versican content. Versican localized preferentially to the vicinity of tumor vasculature and macrophages in the tumor. However, an ADAMTS protease-generated versican fragment uniquely localized to vascular endothelium. To specifically determine the impact of host/stroma-derived versican we therefore compared growth of tumors from B16F10 cells, which produced littleversican, in Vcan hdf/+ mice and wild-type littermates. Tumors in Vcan hdf/+ mice had reduced growth with a lower capillary density and accumulation of capillaries at the tumor periphery. These findings illustrate the variability of tumor cell line expression of versican, and demonstrate that versican is consistently contributed by the stromal tissue, where it contributes to tumor angiogenesis.
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影响因子：
1.5
作者：
Dubail, Johanne;Aramaki-Hattori, Noriko;Bader, Hannah L.;Nelson, Courtney M.;Katebi, Negin;Matuska, Brittany;Olsen, Bjorn R.;Apte, Suneel S.
通讯作者：
Apte, Suneel S.
影响因子：
4.8
作者：
Dutt, S;Kléber, M;Zimmermann, DR
通讯作者：
Zimmermann, DR
影响因子：
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作者：
Carrino, David A.;Calabro, Anthony;Caplan, Arnold I.
通讯作者：
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影响因子：
20.3
作者：
Hope, Chelsea;Foulcer, Simon;Asimakopoulos, Fotis
通讯作者：
Asimakopoulos, Fotis
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.