Naslov
Hedgehog-GLI signaling pathway in 3D model of prostate cancer

Autori
Petrić, Tina ; Kurtović, Matea ; Piteša, Nikolina ; Čonkaš, Josipa ; Musani, Vesna ; Ozretić, Petar ; Sabol, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
From Science to Knowledge / Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2022, 117-117

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology: From Science to Knowledge (HDBMB22)

Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Prostate cancer, HH-GLI signaling pathway, spheroids

Sažetak
Introduction Prostate cancer is the second most frequent cancer diagnosed in men worldwide. Although, radical prostatectomy and radiation have been proven quite effective at the early stages of the disease while tumor is still localized, management of advanced stages is limited due to the development of biological mechanisms of resistance to medication. One of the relevant pathways in prostate cancer progression is the Hedgehog-GLI (HH-GLI) signaling pathway which is crucial for normal embryonic development, stem cell maintenance and tissue homeostasis in adult organisms but its aberrant activation in adult cells has been linked with the development of various tumors, including prostate cancer. The aim of this research was to better understand the differences in HH-GLI signaling pathway in co- culture of prostate cancer and stromal cells in two-dimensional (adherent) and three-dimensional (spheroid) models. Material and method We used adenocarcinoma prostate cell line LNCaP and cancer-associated prostate fibroblasts WPMY-1. For the two- dimensional models, cells were grown together in different ratios (5:1, 2:1, 1:1, 1:2 and 1:5). For the generation of spheroid models, we employed the hanging drop system. The response to HH-GLI signaling pathway inhibition was investigated using four different treatments and observing these cell lines with MTT assay. We have also investigated differences in expression of key genes involved in HH-GLI signaling pathway between cancer and stromal cell lines, both grown in 2- and 3-dimensional system by Real-time PCR. Results and discussion From the results that we obtained by MTT assay, we observed that the best seeding ratio for both cell lines is 1:1, so this ratio was chosen for 3D co- cultures. Cancer and stromal cells are forming spheroids of different shapes and sizes. HH-GLI signaling pathway inhibition showed that the cell death is delayed in the cancer-fibroblast co- culture compared to monocultures. From the analysis of the expression of key genes involved in HH-GLI signaling pathway it is visible that stromal cells are changing their characteristics to the higher extent compared to the cancer cell lines. Conclusion Results obtained so far are pointing out the importance of interaction between the cancer cells and cancer associated fibroblast in the prostate cancer progression. It is known that tumor-stroma interaction is crucial for Hedgehog signaling in the prostate, but here we demonstrate the resistance of co-culture compared to monocultures on an in vitro model.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA