Naslov
3D culture of prostate cancer as a model to study hedgehog-gli signaling pathway

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
“HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation : Book of Abstracts / Ozretić, Petar - Zagreb : Hrvatsko društvo za istraživanje raka (HDIR), 2022, 44-44

ISBN
978-953-48672-1-1

Skup
6th Meeting of the Croatian Association for Cancer Research with International Participation: Targeting Cancer (HDIR-6)

Mjesto i datum
Zagreb, Hrvatska, 10.11.2022. - 12.11.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

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

Sažetak
Prostate cancer is the second most frequent cancer diagnosed in men worldwide. Albeit radical prostatectomy and radiation have been proven as quite effective strategies to fight the tumor while 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. We used adenocarcinoma prostate cell line LNCaP and cancer-associated prostate fibroblasts WPMY-1. For the two-dimensional models, cells were co-cultured in different ratios (5:1, 2:1, 1:1, 1:2 and 1:5). For the generation of spheroid models, the hanging drop system was employed and cells were co- cultured in the same ratios as 2D models. The response to HH-GLI signaling pathway inhibition was investigated using four different treatments and observing these cell lines with MTT assay. Differences in expression of key genes involved in HH-GLI signaling pathway were also analyzed between cancer and stromal cell lines, both grown in 2- and 3-dimensional system by Real-time PCR. Results demonstrated that 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 line. 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-GLI 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

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