Merkel cell carcinoma expresses vasculogenic mimicry: demonstration in patients and experimental manipulation in xenografts.
Merkel cell carcinoma expresses vasculogenic mimicry: demonstration in patients and experimental manipulation in xenografts.
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DOI：
10.1038/labinvest.2014.99
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发表时间：
2014-10
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影响因子：
--
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中科院分区：
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--
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默克尔细胞癌（MCC）是一种高毒性皮肤肿瘤，像黑色素瘤一样，是患者发病率和死亡率的常见原因。负责MCC的攻击行为的细胞机制仍然未知。血管生成拟态（VM）是一种与癌症毒力相关的现象，包括在黑色素瘤中，其中与表达某些内皮基因的肿瘤细胞相关的层粘连蛋白网络形成。为了确定VM是否是MCC中的一个因素，我们采用了使用两个独立的人MCC系的相关异种移植模型。实验诱导的肿瘤在组织学上与患者MCC非常相似，并且两者都含有与血管内皮-钙粘蛋白（CD 144）和血管内皮生长因子受体1（VEGFR-1）相关的层粘连蛋白网络以及黑色素瘤中VM典型的Nodal表达。此外，两种已建立的用于人MCC的化疗剂，依托泊苷和卡铂，在全身给药后诱导异种移植物坏死，同时在持续存在的明显耐药的存活肿瘤区域中富集层粘连蛋白网络。这些发现首次建立了VM样层粘连蛋白网络作为MCC中的生物标志物，证明了MCC异种移植模型的实验效用，并表明MCC的VM富集区域可能对常规化疗药物无效。
Merkel cell carcinoma (MCC) is a highly virulent cutaneous neoplasm that, like melanoma, is a frequent cause of patient morbidity and mortality. The cellular mechanisms responsible for the aggressive behavior of MCC remain unknown. Vasculogenic mimicry (VM) is a phenomenon associated with cancer virulence, including in melanoma, whereby anastomosing laminin networks form in association with tumor cells that express certain endothelial genes. To determine whether VM is a factor in MCC, we employed a relevant xenograft model using two independent human MCC lines. Experimentally induced tumors were remarkably similar histologically to patient MCC, and both contained laminin networks associated with vascular endothelial-cadherin (CD144) and vascular endothelial growth factor receptor 1 (VEGFR-1) as well as Nodal expression typical of VM in melanoma. Moreover, two established chemotherapeutic agents utilized for human MCC, etoposide and carboplatin, induced necrosis in xenografts upon systemic administration while enriching for laminin networks in apparently resistant viable tumor regions that persisted. These findings for the first time establish VM-like laminin networks as a biomarker in MCC, demonstrate the experimental utility of the MCC xenograft model, and suggest that VM-rich regions of MCC may be refractory to conventional chemotherapeutic agents.
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影响因子：
13.8
作者：
Akhtar, S;Oza, KK;Wright, J
通讯作者：
Wright, J
血管生成拟态是喉鳞状细胞癌的关键预后因素：一种新的血液供应模式
影响因子：
6.1
作者：
Lin Peng;Wang Wei;Zhang Jin-mei
通讯作者：
Zhang Jin-mei
影响因子：
11.2
作者：
Frank, NY;Margaryan, A;Frank, MH
通讯作者：
Frank, MH
DOI：
10.1007/s11596-013-1129-4
发表时间：
2013-06-01
影响因子：
--
作者：
Chai, Da-min;Bao, Zheng-qi;Tao, Yi-sheng
通讯作者：
Tao, Yi-sheng
DOI：
10.1083/jcb.201102147
发表时间：
2012-02-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lu P;Weaver VM;Werb Z
通讯作者：
Werb Z