Basement membrane as a spatial organizer of polarized epithelia. Exogenous basement membrane reorients pancreatic epithelial tumor cells in vitro.
Basement membrane as a spatial organizer of polarized epithelia. Exogenous basement membrane reorients pancreatic epithelial tumor cells in vitro.
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发表时间：
1986
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通讯作者：
D. Ingber;J. Madri;J. Jamieson
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作者：
D. Ingber;J. Madri;J. Jamieson
作者先前描述了一种可移植的胰腺腺泡癌，它包含只有在体内与基底膜(BM)接触时才能重组和显示正常上皮取向的细胞。在目前的研究中，他们调查了外源性脱细胞骨髓或胶原基质(从人羊膜制备)是否足以在体外重新定位胰腺腺泡肿瘤细胞。机械分散的肿瘤细胞不能自发地附着在标准培养底物上，但它们却附着在外源完整的BM上，或者贴附于涂有提纯的层粘连蛋白或IV型胶原的培养皿上。细胞与羊膜BM接触导致肿瘤细胞形态改变，细胞内肌动蛋白组装成纤维束，并恢复正常的上皮细胞与细胞之间的相互作用。计算机形态计量学证实，在BM上培养6小时内，肿瘤细胞呈现出正态极化分布的脂滴、核、高尔基复合体和酶原颗粒(从底部到顶部)。尽管完整的连接复合体和不同的膜结构域没有发生改变，但仅在肿瘤细胞顶端表面观察到粘附带和微绒毛。在没有蛋白质合成(25微克/毫升放线菌胺)的情况下，也发生了类似的附着、细胞骨架改变和重新定位。相反，保留在羊膜基质上的肿瘤细胞仍然是圆形的，显示出肌动蛋白的环状环，并呈现随机定向。因此，BM通常用于整合和维持极化上皮内的单个细胞。
The authors have previously described a transplantable pancreatic acinar carcinoma that comprises cells which reorganize and display normal epithelial orientation only when in contact with basement membrane (BM) in vivo. In the present study, they investigated whether exogenous acellular BM or collagenous stroma (prepared from human amnion) was sufficient to reorient pancreatic acinar tumor cells in vitro. Mechanically dispersed tumor cells could not spontaneously attach to standard culture substrata; yet they adhered to exogenous intact BM or to dishes coated with purified laminin or Type IV collagen. Cell contact with amniotic BM resulted in tumor cell shape changes, assembly of intracellular actin into fibrous bundles, and restoration of normal epithelial cell-cell interactions. Computerized morphometry confirmed that tumor cells exhibited a normal polarized distribution of lipid droplets, nuclei, Golgi complexes, and zymogen granules (from base to apex) within 6 hours of culture on BM. Adhering zonules and microvilli were observed only along apical tumor cell surfaces, although full junctional complexes and distinct membrane domains did not reform. Similar attachment, cytoskeletal alterations, and reorientation occurred in the absence of protein synthesis (25 micrograms/ml cycloheximide). In contrast, tumor cells that were maintained on amniotic stroma remained round, displayed circumferential rings of actin, and appeared randomly oriented. Thus, BM may normally serve to integrate and maintain individual cells within a polarized epithelium.