Tumorigenesis and Neoplastic Progression Integrin v Expression Is Required for the Acquisition of a Metastatic Stem / Progenitor Cell Phenotype in Human Prostate Cancer
Tumorigenesis and Neoplastic Progression Integrin v Expression Is Required for the Acquisition of a Metastatic Stem / Progenitor Cell Phenotype in Human Prostate Cancer
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发表时间：
2011
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通讯作者：
C. V. D. Hoogen;G. Horst;H. Cheung;J. Buijs;R. Pelger;G. Pluijm
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作者：
C. V. D. Hoogen;G. Horst;H. Cheung;J. Buijs;R. Pelger;G. Pluijm
整合素参与多种细胞过程，包括细胞粘附、迁移、增殖、存活和生长因子受体的活化。最近的研究表明，与更分化的、定向的前体细胞相比，在前列腺癌干/祖细胞亚群中v整合素的表达升高。在这里，我们研究的功能作用，v整合素受体表达在收购的转移干/祖细胞表型在人前列腺癌。PC-3 M-Pro4前列腺癌细胞中v整合素表达的稳定敲除与前列腺癌干/祖细胞特征（2整合素、CD 44和ALDH）的显著降低以及侵袭相关基因Snail、Snail 2和Twist的表达降低相一致。与这些观察结果一致，vknockdown在体外强烈抑制人前列腺癌细胞的克隆形成和迁移潜力，并在原位生长和骨转移的临床前模型中显著降低致瘤性和转移能力。我们的数据表明，整合素V的表达在功能上参与维持一个高度迁移，间充质细胞表型，以及收购的干/祖细胞表型在人前列腺癌细胞转移启动能力。(Am J Pathol 2011，179：2559-2568; DOI：10.1016/j.ajpath.2011.07.011）
Integrins participate in multiple cellular processes, including cell adhesion, migration, proliferation, survival, and the activation of growth factor receptors. Recent studies have shown that expression of v integrins is elevated in the prostate cancer stem/progenitor cell subpopulation compared with more differentiated, committed precursors. Here, we examine the functional role of v integrin receptor expression in the acquisition of a metastatic stem/progenitor phenotype in human prostate cancer. Stable knockdown of v integrins expression in PC-3M-Pro4 prostate cancer cells coincided with a significant decrease of prostate cancer stem/progenitor cell characteristics ( 2 integrin, CD44, and ALDH) and decreased expression of invasion-associated genes Snail, Snail2, and Twist. Consistent with these observations, vknockdown strongly inhibited the clonogenic and migratory potentials of human prostate cancer cells in vitro and significantly decreased tumorigenicity and metastatic ability in preclinical models of orthotopic growth and bone metastasis. Our data indicate that integrin v expression is functionally involved in the maintenance of a highly migratory, mesenchymal cellular phenotype as well as the acquisition of a stem/ progenitor phenotype in human prostate cancer cells with metastasis-initiating capacity. (Am J Pathol 2011, 179:2559–2568; DOI: 10.1016/j.ajpath.2011.07.011)