Exploring the role of senescence in oral carcinogenesis

Presentation: P010
Topic: Cancer Biology
Type: Poster
Authors: Jessica Bourbonnais, MSc1; Francis Rodier, PhD1; Apostolos Christopoulos, MD, MSc2
Institution(s): 1Institut du Cancer de Montréal, CRCHUM; 2CHUM

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that encompasses many anatomical sites, who together have a 60% 5-year survival rate. However, each type of HNSCC differs from one another. Risks factors and underlying mechanisms of carcinogenesis can inevitably influence response to treatments and survival rates. Oral squamous cell carcinoma (OSCC) accounts for the majority of HNSCC and has a relatively high level of recurrency, varying from 25-60% depending on the stage at the time of diagnosis. Consequently, OSCC has a 45% 5-year survival rate, a rate significantly lower than the all-inclusive HNSCC. Oral carcinogenesis involves many steps of transformation within the epithelial cells themselves and the surrounding microenvironment. Although the genetic landscape surrounding the varying stages of transformed mucosal epithelial cells has been well documented, there is a lack of understanding when it comes to the role of the microenvironment. Specifically, the role of senescent cells in oral carcinogenesis and cancer progression has yet to be well defined. Senescence is a state of stable proliferation arrest in which a cell can enter in response to a genotoxic stress through the p53-p21 or the pRB-p16 pathways. This state of proliferation arrest will prevent the damaged cells from dividing, therefore protecting against further mutation accumulation. However, senescence is a double-edged sword. In fact, senescent cells have a secretory phenotype composed of many molecules that promote proliferation, migration and invasion of tumor cells, which in turn accelerates cancer progression. High levels of p53 have been detected in the oral mucosa surrounding OSCC, suggesting the presence of senescent cells. My project is to determine the role of senescence in oral carcinogenesis and progression. In order to do so, we have started by evaluating the effects of different senescent cells on OSCC cell lines. Currently, we are co-culturing OSCC cell lines with senescent epithelial cells, with or without fibroblasts. We will then assess the impact of these senescent cells on OSCC by measuring proliferation, migration and invasiveness. Moreso, we will also evaluate fibroblast transformation within this context by measuring cancer-associated fibroblast markers (a-SMA and PDGFb-R) and senescent markers (p21, p17 and lamin-B1) through western blot. In the following months, we will acquire different oral mucosa cell lines at varying stages of carcinogenesis and repeat these preliminary experiments within the same context. However, we will evaluate markers in these pre-neoplastic cell lines indicative of early carcinogenesis progression (PI3K pathway, DCBLD1 and ki67 overexpression). In conclusion, we will be sharing these impending results at this year's AHNS conference.