trychoepithelioma, rhabdomyosarcoma, digestive tract tumors, prostate tumors, small-cell lung cancer, squamous lung cancer, pancreatic cancer, breast cancer and ovarian cancer (10). The role of Hh-Gli signaling in ovarian development and malignancy

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.