Shen Xiaoli, Rychahou Piotr G, Evers B Mark, Falzon Miriam
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Cancer Lett. 2007 Dec 18;258(2):241-52. doi: 10.1016/j.canlet.2007.09.010. Epub 2007 Oct 26.
Parathyroid hormone-related protein (PTHrP) is expressed by human colon cancer tissue and cell lines. Expression of PTHrP and phosphatidylinositol 3-kinase (PI3-K) pathway components correlates with the severity of colon carcinoma. Here we observed a positive effect of endogenous PTHrP on LoVo (human colon cancer) cell proliferation, migration, invasion, integrin alpha6 and beta4 expression, and p-Akt levels. There was a direct correlation between PTHrP expression and anchorage-independent cell growth. PTHrP significantly increased xenograft growth; tumors from PTHrP-overexpressing cells showed increased expression of integrins alpha6 and beta4, and PI3-K pathway components. The higher expression of PTHrP in human colon cancer adenocarcinoma vs. normal colonic mucosa was accompanied by increased integrin alpha6 and beta4 levels. Elevated PTHrP expression in colon cancer may thus upregulate integrin alpha6beta4 expression, with consequent PI3-K activation. Targeting PTHrP might result in effective inhibition of tumor growth, migration, and invasion.
甲状旁腺激素相关蛋白(PTHrP)在人结肠癌组织和细胞系中表达。PTHrP和磷脂酰肌醇3激酶(PI3-K)信号通路成分的表达与结肠癌的严重程度相关。在此,我们观察到内源性PTHrP对LoVo(人结肠癌)细胞增殖、迁移、侵袭、整合素α6和β4表达以及p-Akt水平具有正向作用。PTHrP表达与非锚定依赖性细胞生长之间存在直接关联。PTHrP显著增加异种移植瘤的生长;过表达PTHrP的细胞所形成的肿瘤显示整合素α6和β4以及PI3-K信号通路成分的表达增加。与正常结肠黏膜相比,人结肠腺癌中PTHrP的高表达伴随着整合素α6和β4水平的升高。因此,结肠癌中PTHrP表达的升高可能上调整合素α6β4的表达,从而激活PI3-K。靶向PTHrP可能有效抑制肿瘤的生长、迁移和侵袭。