The human myoepithelial cell is a natural tumor suppressor.
The human myoepithelial cell is a natural tumor suppressor.
复制标题
DOI：
--
复制
发表时间：
1997-11
期刊：
影响因子：
--
通讯作者：
M. Sternlicht;P. Kedeshian;Z. Shao;S. Safarians;S. Barsky
中科院分区：
文献类型：
--
作者：
M. Sternlicht;P. Kedeshian;Z. Shao;S. Safarians;S. Barsky
肌上皮细胞包围着腺管和腺泡，形成一个天然的边界，将增殖的上皮细胞与基底膜和下面的基质隔开。原位和体外肌上皮细胞组成性表达大量的蛋白酶抑制剂，包括金属蛋白酶1的组织抑制剂、蛋白酶连接蛋白-II、α-1抗胰蛋白酶和maspin。我们实验室建立的人肌上皮异种移植物（HMS-X、HMS-3X和HMS-4X）积累了丰富的含有隔离蛋白酶抑制剂的细胞外基质。Humatrix是一种我们从HMS-X衍生的凝胶，可抑制肿瘤细胞的侵袭（降至Matrigel对照的25% +/-10%; P < 0.01），我们最近建立的人肌上皮细胞系HMS-1、HMS-3和HMS-4在细胞侵袭中抑制肿瘤细胞侵袭，（降至对照的42% +/-7%; P < 0.05）和条件培养基测定（降至对照的30% +/-8%; P < 0.01）。HMS-1、HMS-3和HMS-4的抗侵袭作用可以通过maspin依赖性机制被佛波醇12-肉豆蔻酸酯13-乙酸酯增强（降至对照的2% +/-1%），并且通过maspin非依赖性机制被地塞米松消除（高达对照的95% +/-5%）（P < 0.01）。HMS-X、HMS-3X、HMS-4X和Humatrix对严重联合免疫缺陷小鼠的肿瘤侵袭和转移均有抑制作用（P < 0.001）。累积数据表明，肌上皮细胞是侵袭和转移的天然旁分泌抑制因子，并且可以特异性地抑制癌前疾病状态在体内向侵袭性癌症的进展。
Myoepithelial cells, which surround ducts and acini of glandular organs, form a natural border separating proliferating epithelial cells from basement membrane and underlying stroma. Myoepithelial cells in situ and in vitro constitutively express high amounts of proteinase inhibitors that include tissue inhibitor of metalloproteinase 1, protease nexin-II, alpha-1 antitrypsin, and maspin. Human myoepithelial xenografts (HMS-X, HMS-3X, and HMS-4X), which our laboratory has established, accumulate an abundant extracellular matrix containing sequestered proteinase inhibitors. Humatrix, a gel that we have derived from HMS-X, inhibits tumor cell invasion (down to 25% +/- 10% of Matrigel control; P < 0.01), and our recently established human myoepithelial cell lines, HMS-1, HMS-3, and HMS-4, inhibit tumor cell invasion in cellular invasion (down to 42% +/- 7% of control; P < 0.05) and in conditioned media assays (down to 30% +/- 8% of control; P < 0.01). The anti-invasive effects of HMS-1, HMS-3, and HMS-4 can be enhanced by phorbol 12-myristate 13-acetate (down to 2% +/- 1% of control) by a maspin-dependent mechanism and abolished by dexamethasone (up to 95% +/- 5% of control) by a maspin-independent mechanism (P < 0.01). HMS-X, HMS-3X, HMS-4X, and Humatrix inhibit tumor invasion and metastasis in severe combined immunodeficient mice (P < 0.001). The cumulative data suggest that myoepithelial cells are natural paracrine suppressors of invasion and metastasis and may specifically inhibit the progression of precancerous disease states to invasive cancer in vivo.