Tumor-stroma co-evolution in prostate cancer progression and metastasis.
Tumor-stroma co-evolution in prostate cancer progression and metastasis.
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DOI：
10.1016/j.semcdb.2009.11.016
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发表时间：
2010-02
影响因子：
7.3
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Josson S;Matsuoka Y;Chung LW;Zhau HE;Wang R
癌症的发展是复杂的，涉及几层相互作用和导致进展的多效性信号传导机制。癌细胞与转移部位的驻留基质成纤维细胞、平滑肌细胞、巨噬细胞、内皮细胞、神经元和迁移细胞相关，并在表型和基因型上激活它们。这些通过激活的细胞信号传导机制成为癌细胞群落的组成部分。在此过程中，癌细胞和癌症微环境中的细胞部分由于氧化应激而“共同进化”，并获得模仿其他细胞类型（其可称为骨模拟、血管模拟、神经模拟和干细胞模拟）的能力，并经历从上皮到间充质的转变，具有明确的行为改变。在我们的实验室中，我们证明了前列腺癌细胞在其基因型和表型特征方面与基质共同进化，并获得拟骨特性，使其能够在骨骼中增殖和存活，作为骨转移。已描述了骨微环境中由活性氧、可溶性和膜结合因子（如超氧化物、β 2微球蛋白和RANKL）介导的几种信号相互作用。靶向癌症相关基质微环境中的信号传导途径与已知的常规治疗方式相结合，可能对癌症治疗产生协同效应。由于癌细胞不断相互作用并获得主要由其微环境指导的适应性和生存变化，因此重要的是描述这些相互作用并共同靶向癌症和基质以改善癌症患者的治疗和总体生存。
Cancer development is complex and involves several layers of interactions and pleotropic signalling mechanisms leading to progression. Cancer cells associate with resident stromal fibroblasts, smooth muscle cells, macrophages, endothelium, neurons and migrating cells at metastatic sites and phenotypically and genotypically activate them. These become an integral part of the cancer cell community through activated cell signalling mechanisms. During this process, the cancer cells and cells in the cancer microenvironment “co-evolve” in part due to oxidative stress, and acquire the ability to mimic other cell types (which can be termed osteomimicry, vasculomimicry, neuromimicry and stem cell mimicry), and undergo transition from epithelium to mesenchyme with definitive behavioral modifications. In our laboratory, we demonstrated that prostate cancer cells co-evolve in their genotypic and phenotypic characters with stroma and acquire osteomimetic properties allowing them to proliferate and survive in the skeleton as bone metastasis. Several signalling interactions in the bone microenvironment, mediated by reactive oxygen species, soluble and membrane bound factors, such as superoxide, β2microglobulin and RANKL have been described. Targeting the signalling pathways in the cancer-associated stromal microenvironment in combination with known conventional therepeutic modalities could have a synergistic effect on cancer treatment. Since cancer cells are constantly interacting and acquiring adaptive and survival changes primarily directed by their microenvironment, it is important to delineate these interactions and co-target both cancer and stroma to improve the treatment and overall survival of cancer patients.
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悬浮在胶原蛋白凝胶中的上皮可以失去极性，并表达迁移间充质细胞的特征。
影响因子：
7.8
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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