Investigating the involvement of FGFR signalling in cervical cancer using a 3D organotypic model

Cervical cancer is one of the most preventable yet the most common malignancies among women worldwide. Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a vital role in controlling cell survival, proliferation and cell migration and some cancer cells hijack aspects of this pathway to gain control over growth and motility. Appropriate cellular models, representing various aspects of cervical cancer, will enhance our understanding of cancer biology and therefore, improve the treatment options. The co-culturef in vitro 3D organotypic model of cervical cancer and stromal cells grown within, models the cervical cancer more realistically than 2D culture. Such cultures have been used to study the development and repair of the epidermis and to understand the progression and stromal invasion of different types of cancers. The aim of the study was to construct a 3D organotypic model of cervical cancer in order to investigate the FGF(R) signaling in cervical cancer cell lines (HeLa, SiHa, CaSki) and a human keratinocyte cell line (HaCaT) as a control. The 3D organotypic model was constructed using the HFF-2 fibroblasts as stroma equivalent and growing the cancer cells, with or without PD173074, for 12 days in an air-liquid interface. Cultures were fixed, embedded in paraffin, and sections stained with epithelial tissue differentiation markers, epithelial mesenchymal transition (EMT) markers, FGFR-1 and 2, FGF2, Granzyme B (GrB), HPV, Ki67. Cultures stained using immunohistochemistry were negative for some epithelial markers however, they were positive for vimentin and N-cadherin suggesting that the cells had undergone EMT. Ki67 expression was also inhibited in SiHa cultures treated with PD173074. Cervical cancer organotypic models have been established and characterized using three different cervical cancer cell lines that can be used to study the FGF(R) expression in a more realistic environment. The initial data suggests that FGFR Signaling is important in cervical cancer progression