Klezovitch Olga, Chevillet John, Mirosevich Janni, Roberts Richard L, Matusik Robert J, Vasioukhin Valeri
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancer Cell. 2004 Aug;6(2):185-95. doi: 10.1016/j.ccr.2004.07.008.
The majority of cancer-related deaths are associated with metastasis; however, little is known about the mechanisms of this process. Hepsin is a cell surface serine protease that is markedly upregulated in human prostate cancer; however, the functional significance of this upregulation is unknown. We report here that hepsin overexpression in prostate epithelium in vivo causes disorganization of the basement membrane. Overexpression of hepsin in a mouse model of nonmetastasizing prostate cancer has no impact on cell proliferation, but causes disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis to liver, lung, and bone. We provide in vivo evidence that upregulation of a cell surface serine protease in a primary tumor promotes cancer progression and metastasis.
大多数与癌症相关的死亡都与转移有关；然而，对于这一过程的机制却知之甚少。Hepsin是一种细胞表面丝氨酸蛋白酶，在人类前列腺癌中显著上调；然而，这种上调的功能意义尚不清楚。我们在此报告，体内前列腺上皮中hepsin的过表达会导致基底膜紊乱。在非转移性前列腺癌小鼠模型中，hepsin的过表达对细胞增殖没有影响，但会导致基底膜紊乱，并促进原发性前列腺癌进展以及向肝脏、肺和骨转移。我们提供了体内证据，表明原发性肿瘤中细胞表面丝氨酸蛋白酶的上调会促进癌症进展和转移。
