Transforming growth factor β1 induces squamous carcinoma cell variants with increased metastatic abilities and a disorganized cytoskeleton
Transforming growth factor β1 induces squamous carcinoma cell variants with increased metastatic abilities and a disorganized cytoskeleton
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DOI：
10.1006/excr.1998.4219
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发表时间：
1998-11-01
影响因子：
3.7
通讯作者：
Quintanilla, M
中科院分区：
文献类型：
--
作者：
Frontelo, P;González-Garrigues, M;Quintanilla, M
先前的研究表明，当在TGF-β存在下培养时，小鼠转化的角质形成细胞经历上皮-成纤维细胞转化（1）。这种转化在体内与鳞状梭形癌转变有关。我们从用TGF-β处理后的鳞状细胞癌细胞系（PDV）中获得上皮样（A6，FPA 6）和梭形（B5）克隆细胞变体（1）。从携带AG肿瘤的小鼠的腹水中分离FPA 6细胞。在裸鼠中产生的FPA 6和A6细胞系具有鳞状和低分化成分的混合癌。这两种细胞系共表达角蛋白和波形蛋白，并合成E-钙粘蛋白蛋白，但在早期传代培养的FPA 6细胞（FPA 6-ep）的E-钙粘蛋白mRNA水平降低，角蛋白K8（恶性进展的标志物）的合成增加。免疫荧光分析显示，FPA 6-EP细胞表现出一个混乱的细胞骨架与角蛋白形成局灶性的核外聚集体和F-肌动蛋白应力纤维和皮质束的损失，和E-钙粘蛋白定位于细胞质的细胞接触区域。A6和PDV培养物中的散在细胞也呈现这些异常角蛋白结构，表明FPA 6细胞起源于转移到腹膜腔的A6肿瘤细胞亚群。对细胞系的自发和实验转移潜能的分析表明，与非转移性PDV相比，上皮样和成纤维细胞变体具有获得性转移能力。FPA 6-ep细胞系表现出高度攻击性行为，在将细胞静脉内注射到无胸腺小鼠中后约17天对动物进行计费。FPA 6-EP细胞的表型是不稳定的，并在以后的传代中恢复，其中角蛋白和F-肌动蛋白在细丝中的正常组织和在细胞-细胞接触处的E-钙粘蛋白的定位被恢复。这种表型逆转伴随着FPA 6细胞实验转移潜力的降低而发生。(C)北京：科学出版社.
Previous studies indicated that mouse transformed keratinocytes undergo an epithelial-fibro-blastic conversion when cultured in the presence of TGF-beta(1). This conversion is associated in vivo with a squamous-spindle carcinoma transition. We derived epithelioid (A6, FPA6) and spindle (B5) clonal cell variants from a squamous carcinoma cell line (PDV) after treatment with TGF-beta(1). FPA6 cells were isolated from the ascites fluid of an AG-tumor-bearing mouse. FPA6 and A6 cell lines produced in nude mice mixed carcinomas with a squamous and poorly differentiated component. Both cell lines coexpressed keratins and vimentin and synthesized E-cadherin protein, although FPA6 cells cultured at early passages (FPA6-ep) had reduced levels of E-cadherin mRNA and increased synthesis of keratin K8, a marker of malignant progression. Immunofluorescence analysis revealed that FPA6-ep cells exhibited a disorganized cytoskeleton with keratins forming focal juxtanuclear aggregates and loss of F-actin stress fibers and cortical bundles, and E-cadherin was localized in the cytoplasm out of cell-cell contact areas. Sporadic cells in A6 and PDV cultures also presented those anomalous keratin structures, suggesting that FPA6 cells originated from a subpopulation of A6 tumor cells that metastasized into the peritoneal cavity. The analysis of the spontaneous and experimental metastatic potentials of the cell lines showed that epithelioid and fibroblastic cell variants had acquired metastatic abilities compared to PDV which was nonmetastatic. The FPA6-ep cell line exhibited a highly aggressive behavior, Billing the animals at about 17 days after intravenous injection of the cells into athymic mice. The phenotype of FPA6-ep cells was unstable and reverted at later passages in which the normal organization of keratin and F-actin in filaments and the localization of E-cadherin at cell-cell contacts were restored. This phenotypic reversion occurred concomitantly with a reduction of the experimental metastatic potential of FPA6 cells. (C) 1998 Academic Press.