The peritoneal tumour microenvironment of high-grade serous ovarian cancer.
The peritoneal tumour microenvironment of high-grade serous ovarian cancer.
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DOI：
10.1002/path.4002
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发表时间：
2012-06
影响因子：
7.3
通讯作者：
Balkwill, Frances R.
中科院分区：
文献类型：
--
作者：
Leinster, D. Andrew;Kulbe, Hagen;Everitt, Gemma;Thompson, Richard;Perretti, Mauro;Gavins, Felicity N. E.;Cooper, Dianne;Gould, David;Ennis, Darren P.;Lockley, Michelle;McNeish, Iain A.;Nourshargh, Sussan;Balkwill, Frances R.
高级别浆液性卵巢癌（HGSC）早期广泛扩散到整个腹膜间隙，导致多发性病变，这是一个主要的临床问题。本研究的目的是研究患者活检组织中腹膜肿瘤沉积物的细胞组成及其在小鼠模型中的演变，使用免疫组织化学，活体显微镜，共聚焦显微镜和3D建模。来自HGSC患者网膜的肿瘤沉积物含有显著的CD 3 + T细胞和CD 68+巨噬细胞的白细胞浸润，偶尔有中性粒细胞。α-平滑肌肌动蛋白+（α-SMA+）周细胞和/或成纤维细胞包围这些血管化良好的肿瘤沉积物。使用小鼠肠肠系膜作为可以容易地成像的可接近小鼠腹膜组织，以及两种不同的可移植模型，我们在腹膜内注射恶性细胞后发现了多个显微肿瘤沉积物。腹膜表面附着迅速（6-48 h），48 h时可见广泛的CD 45+白细胞浸润。这种浸润持续至终点，在同基因鼠ID 8模型中，主要由CD 3 + T淋巴细胞和CD 68+巨噬细胞组成，α-SMA+细胞也从最早期开始参与。大多数肿瘤沉积物在现有的肠系膜血管上方发展，但在IGF-I异种移植物中2-3周和ID 8同基因模型中6周时，在无血管空间中新血管朝向肿瘤沉积物追踪;在终点时建立了有力的回旋血液供应。通过在IGROV-1细胞中稳定表达针对CXCR 4的shRNA来抑制肿瘤细胞因子的产生，不会影响细胞与系膜的附着，但会延迟新血管形成并减少肿瘤存款大小。我们得出结论，在HGSC患者中发现的多个腹膜肿瘤沉积物可以在小鼠中建模。这里描述的技术可能是有用的，以评估治疗的目标，这种疾病的传播阶段。版权所有© 2012大不列颠及爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3+ T cells and CD68+ macrophages, with occasional neutrophils. Alpha-smooth muscle actin+ (α-SMA+) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6–48 h) with an extensive CD45+ leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3+ T lymphocytes and CD68+ macrophages with α-SMA+ cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2–3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1038/nrc3144
发表时间：
2011-09-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Chien, Jeremy R.;Aletti, Giovanni;Hartmann, Lynn C.
通讯作者：
Hartmann, Lynn C.
DOI：
10.1073/pnas.0509182102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Sato, E;Olson, SH;Odunsi, K
通讯作者：
Odunsi, K
卵巢癌中上皮和间充质标记的分析揭示了表型异质性和可塑性。
影响因子：
3.7
作者：
Strauss R;Li ZY;Liu Y;Beyer I;Persson J;Sova P;Möller T;Pesonen S;Hemminki A;Hamerlik P;Drescher C;Urban N;Bartek J;Lieber A
通讯作者：
Lieber A