Voll Eric A, Ogden Irene M, Pavese Janet M, Huang XiaoKe, Xu Li, Jovanovic Borko D, Bergan Raymond C
Department of Medicine, Northwestern University, 303 E Superior, Chicago, IL.
Oncotarget. 2014 May 15;5(9):2648-63. doi: 10.18632/oncotarget.1917.
Prostate cancer (PCa) is the most common form of cancer in American men. Mortality from PCa is caused by the movement of cancer cells from the primary organ to form metastatic tumors at distant sites. Heat shock protein 27 (HSP27) is known to increase human PCa cell invasion and its overexpression is associated with metastatic disease. The role of HSP27 in driving PCa cell movement from the prostate to distant metastatic sites is unknown. Increased HSP27 expression increased metastasis as well as primary tumor mass. In vitro studies further examined the mechanism of HSP27-induced metastatic behavior. HSP27 did not affect cell detachment, adhesion, or migration, but did increase cell invasion. Cell invasion was dependent upon matrix metalloproteinase 2 (MMP-2), whose expression was increased by HSP27. In vivo, HSP27 induced commensurate changes in MMP-2 expression in tumors. These findings demonstrate that HSP27 drives metastatic spread of cancer cells from the prostate to distant sites, does so across a continuum of expression levels, and identifies HSP27-driven increases in MMP-2 expression as functionally relevant. These findings add to prior studies demonstrating that HSP27 increases PCa cell motility, growth and survival. Together, they demonstrate that HSP27 plays an important role in PCa progression.
前列腺癌（PCa）是美国男性中最常见的癌症形式。PCa导致的死亡是由癌细胞从原发器官转移至远处部位形成转移性肿瘤所致。已知热休克蛋白27（HSP27）会增强人类PCa细胞的侵袭能力，其过表达与转移性疾病相关。HSP27在促使PCa细胞从前列腺转移至远处转移部位过程中所起的作用尚不清楚。HSP27表达增加会导致转移以及原发性肿瘤增大。体外研究进一步探究了HSP27诱导转移行为的机制。HSP27不影响细胞脱离、黏附或迁移，但会增加细胞侵袭。细胞侵袭依赖于基质金属蛋白酶2（MMP - 2），其表达受HSP27上调。在体内，HSP27会使肿瘤中MMP - 2表达发生相应变化。这些发现表明，HSP27促使癌细胞从前列腺转移至远处部位，在连续的表达水平上均如此，并确定HSP27驱动的MMP - 2表达增加具有功能相关性。这些发现补充了先前的研究，即HSP27会增强PCa细胞的运动性、生长和存活能力。总之，它们表明HSP27在PCa进展中起重要作用。
