Division of Molecular Medicine, Rudjer Boskovic Institute, 10002 Zagreb, Croatia.
Int J Oncol. 2012 Oct;41(4):1411-8. doi: 10.3892/ijo.2012.1554. Epub 2012 Jul 13.
The Hedgehog-Gli (Hh-Gli) signaling pathway was examined in ovarian dermoids, which show characteristics of both tumors and developmental malformations. Dermoids are classified as mature teratomas that present differentiation into various tissues, mostly epidermal elements such as glands, multilayered epithelium, hair follicles and occasionally bone and cartilage. Their development is attributed to aberrant meiosis of germinal cells within the ovary. We showed activation of the Hh-Gli signaling in ovarian dermoid primary cultures. Cyclopamine treatment slows down cell proliferation, while the Sonic Hedgehog (Shh) protein stimulates cell proliferation and induces internalization of the Patched (Ptch) protein, which accumulates in the form of granules in the cytoplasm, colocalized with the Shh protein. Cyclopamine treatment decreases Gli1 localization in the nucleus compared to non-treated cells. Based on our observations, the mechanism of Hedgehog activation in the ovarian dermoids could be the ligand-dependent autocrine pathway, which can also be stimulated by paracrine signals.
Hedgehog-Gli (Hh-Gli) 信号通路在卵巢皮样囊肿中进行了研究，卵巢皮样囊肿具有肿瘤和发育畸形的特征。皮样囊肿被归类为成熟的畸胎瘤，表现出向各种组织的分化，主要是表皮成分，如腺体、复层上皮、毛囊，偶尔还有骨和软骨。它们的发育归因于卵巢内生殖细胞的异常减数分裂。我们显示出卵巢皮样囊肿原代培养物中 Hh-Gli 信号的激活。环巴胺处理减缓细胞增殖，而 Sonic Hedgehog (Shh) 蛋白刺激细胞增殖并诱导 Patched (Ptch) 蛋白内化，该蛋白以颗粒的形式在细胞质中积累，与 Shh 蛋白共定位。与未处理的细胞相比，环巴胺处理导致 Gli1 在核内的定位减少。根据我们的观察，卵巢皮样囊肿中 Hedgehog 的激活机制可能是配体依赖性自分泌途径，也可以被旁分泌信号刺激。
