Nilsson M, Dahlman T, Westermark B, Westermark K
Institute of Anatomy and Cell Biology, University of Gothenburg, Sweden.
Exp Cell Res. 1995 Oct;220(2):257-65. doi: 10.1006/excr.1995.1314.
The regulation of growth and migration of thyroid follicular cells by epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta 1) were studied in primary cultures of porcine thyroid follicles embedded in collagen gel. Cultures were exposed to growth factors and [3H]thymidine (1 microCi/ml) for 3 days and then examined by light microscopic autoradiography. EGF at 1 ng/ml increased the [3H]thymidine labeling index from approximately 1% (control value) to 60% and stimulated fivefold the number of cells invading the collagen matrix. Intermediate responses were seen after treatment with 0.1 ng/ml of EGF. EGF-stimulated [3H]thymidine incorporation was reduced by TGF-beta 1 at concentrations above 0.1 ng/ml. In contrast, TGF-beta 1, which alone only had a minor stimulatory effect on cell motility, markedly promoted the migratory response to EGF (1 ng/ml). Thus, 0.1 ng/ml TGF-beta 1 doubled the fraction of migrating cells without changing the level of [3H]thymidine incorporation. Moreover, cell migration was still fourfold over control values in cultures exposed to 1.0 ng/ml EGF and 1.0 ng/ml TGF-beta 1, despite a strongly inhibited [3H]thymidine labeling. The number of microfollicles located peripherally to the mother follicles was increased synergistically by EGF and TGF-beta 1. The epithelium of mother follicles became grossly discontinuous in regions of intense cell migration induced by EGF and TGF-beta 1 in combination. In conclusion, TGF-beta 1 modulates the response of porcine thyrocytes to EGF in collagen gel cultures by promoting cell migration along with inhibition of [3H]thymidine incorporation. This suggests that EGF stimulates cell motility independent of the mitogenic signal. The persistent loss of epithelial integrity during enhanced cell migration indicates that mechanisms of intercellular adhesiveness are down-regulated by TGF-beta 1 and EGF in cooperation.
在包埋于胶原凝胶中的猪甲状腺滤泡原代培养物中，研究了表皮生长因子（EGF）和转化生长因子-β1（TGF-β1）对甲状腺滤泡细胞生长和迁移的调节作用。将培养物暴露于生长因子和[3H]胸腺嘧啶核苷（1微居里/毫升）3天，然后通过光学显微镜放射自显影进行检测。1纳克/毫升的EGF使[3H]胸腺嘧啶核苷标记指数从约1%（对照值）增加到60%，并使侵入胶原基质的细胞数量增加了五倍。用0.1纳克/毫升的EGF处理后出现中间反应。浓度高于0.1纳克/毫升的TGF-β1可降低EGF刺激的[3H]胸腺嘧啶核苷掺入。相反，单独的TGF-β1对细胞运动仅具有轻微的刺激作用，但能显著促进对EGF（1纳克/毫升）的迁移反应。因此，0.1纳克/毫升的TGF-β1使迁移细胞的比例增加了一倍，而不改变[3H]胸腺嘧啶核苷掺入水平。此外，在暴露于1.0纳克/毫升EGF和1.0纳克/毫升TGF-β1的培养物中，尽管[3H]胸腺嘧啶核苷标记受到强烈抑制，但细胞迁移仍比对照值高四倍。EGF和TGF-β1协同增加了位于母滤泡周围的微滤泡数量。在EGF和TGF-β1联合诱导的强烈细胞迁移区域，母滤泡的上皮变得明显不连续。总之，TGF-β1通过促进细胞迁移并抑制[3H]胸腺嘧啶核苷掺入，调节猪甲状腺细胞在胶原凝胶培养物中对EGF的反应。这表明EGF刺激细胞运动独立于促有丝分裂信号。在增强的细胞迁移过程中上皮完整性的持续丧失表明，TGF-β1和EGF协同下调了细胞间黏附机制。
