Endothelial protein C receptor function in murine and human breast cancer development.
Endothelial protein C receptor function in murine and human breast cancer development.
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DOI：
10.1371/journal.pone.0061071
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ruf W
中科院分区：
文献类型：
--
作者：
Schaffner F;Yokota N;Carneiro-Lobo T;Kitano M;Schaffer M;Anderson GM;Mueller BM;Esmon CT;Ruf W
几种标记物识别癌症干细胞样群体，但对干细胞表面受体在肿瘤进展中的功能作用知之甚少。在这里，我们表明，内皮蛋白C受体（EPCR），造血干细胞，神经元和上皮细胞的标记物，是乳腺癌的原位微环境中的乳腺癌生长至关重要。具有EPCR的亚纯型等位基因的小鼠在自发性乳腺癌发展的PyMT模型中显示出肿瘤生长减少，并且在建立的PyMT肿瘤细胞中缺失EPCR显著减弱了移植的肿瘤摄取和生长。我们发现EPCR+癌症干细胞样群体在侵袭性乳腺脂肪垫增强的人三阴性乳腺癌细胞中扩增。在该模型中，表达EPCR的细胞与另一种以相当频率存在的稳定的祖细胞样亚群相比，具有显著增加的乳腺球和肿瘤细胞起始活性。我们表明，受体阻断抗体EPCR特异性衰减在体内肿瘤生长的EPCR+细胞或EPCR+和EPCR-细胞的异质性混合物启动。此外，我们已经确定了肿瘤相关的巨噬细胞作为EPCR的公认配体的主要来源，这表明了一种新的机制，通过这种机制，肿瘤干细胞样群体受到肿瘤微环境中先天免疫细胞的调节。
Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR+ cells or the heterogenous mixture of EPCR+ and EPCR- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment.
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影响因子：
15.9
作者：
CHAPMAN, HA;ALLEN, CL;FAIR, DS
通讯作者：
FAIR, DS
影响因子：
3.2
作者：
Esmon, Charles T.
通讯作者：
Esmon, Charles T.
影响因子：
3.8
作者：
Anastassiou D;Rumjantseva V;Cheng W;Huang J;Canoll PD;Yamashiro DJ;Kandel JJ
通讯作者：
Kandel JJ
DOI：
10.1164/rccm.201110-1826oc
发表时间：
2012-07-01
影响因子：
24.7
作者：
Anton, Iker;Molina, Eva;Lecanda, Fernando
通讯作者：
Lecanda, Fernando
影响因子：
64.5
作者：
Boire, A;Covic, L;Kuliopulos, A
通讯作者：
Kuliopulos, A