Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.
Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.
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DOI：
10.1371/journal.pone.0085803
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Deftos LJ
中科院分区：
文献类型：
--
作者：
Ongkeko WM;Burton D;Kiang A;Abhold E;Kuo SZ;Rahimy E;Yang M;Hoffman RM;Wang-Rodriguez J;Deftos LJ
甲状旁腺激素相关蛋白 (PTHrP) 具有多种生理和发育功能，并且还已知可促进许多常见癌症的进展，特别是其骨骼侵袭，主要是通过增加骨吸收。本研究的目的是确定 PTHrP 是否可以促进上皮间质转化 (EMT)，这是一个与癌症干细胞有关的过程，在癌症侵袭和转移中发挥着重要作用。在稳定过表达 PTHrP 1-141 或 1-173 亚型的 DU 145 前列腺癌细胞中观察到 EMT，相对于亲代 DU 145，其中 Snail 和波形蛋白上调，E-钙粘蛋白下调。相比之下，在 PC-3 前列腺癌细胞中观察到相反的效果，其中高水平的 PTHrP 通过慢病毒 siRNA 转导被敲低。在 PTHrP 过表达的 DU 145 细胞中观察到肿瘤进展加快，而在 PTHrP 敲低的 PC-3 细胞中观察到肿瘤进展减缓。当原位植入裸鼠时，过表达 PTHrP 的 DU 145 形成更大的肿瘤，并在一种情况下导致脊柱转移，而在注射亲本 DU 145 细胞的小鼠中未观察到这种效应。当注射到裸鼠胫骨中时，PTHrP 过表达的 DU 145 细胞也会引起显着的骨破坏，而亲本 DU 145 细胞几乎不会引起骨破坏。总之，这些结果表明 PTHrP 可能通过 EMT 促进前列腺癌的侵袭性和转移性表型，这是癌症干细胞的重要途径。因此，继续努力阐明 PTHrP 诱导的 EMT 通路以及开发特异性靶向 PTHrP 信号传导的方法可能会带来更有效的前列腺癌治疗方法。
Parathyroid hormone-related protein (PTHrP) possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT), a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer.
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影响因子：
8
作者：
Fortino, V;Torricelli, C;Maioli, E
通讯作者：
Maioli, E
影响因子：
4.7
作者：
Agouni, Abdelali;Sourbier, Carole;Massfelder, Thierry
通讯作者：
Massfelder, Thierry
影响因子：
4.8
作者：
Chan, GK;Deckelbaum, RA;Karaplis, AC
通讯作者：
Karaplis, AC
DOI：
10.1016/j.bbrc.2004.11.162
发表时间：
2005-02-11
影响因子：
3.1
作者：
Deftos, LJ;Barken, I;Geller, J
通讯作者：
Geller, J
影响因子：
15.9
作者：
DELAMATA, J;UY, HL;ROODMAN, GD
通讯作者：
ROODMAN, GD