Research at Bergen Oral Cancer Research Group (BOCG) lead by professor Johannessen, aims to identify molecules of importance for oral cancer development, in order to identify patients at risk for developing oral cancer from premalignant lesions, and to reveal potential targets for more efficient, individualized therapy of oral cancer.
The group’s projects
The major scientific results and research projects of the center:
1. Importance of the heterogeneity of CAFs in OSCC. Bidirectional tumor-stroma interactions have been shown by many to have tumor-promoting effects, but the group focused on the cell interactions within stroma and the functional relevance of heterogeneity of carcinoma-associated fibroblasts (CAFs) for tumor development and invasion. Two distinct CAF subgroups were identified in oral squamous cell carcinoma (OSCC) based on transcriptome analysis of primary cells grown in 3D collagen gels and on the functional analysis of CAF strains derived from several patients with OSCC: 1) a CAF subgroup with a gene expression profile closer to normal fibroblasts, having a more motile phenotype and supporting higher tumor formation and deeper carcinoma cell invasion; and 2) a CAF subgroup with a more divergent gene expression profile, having a more stationary phenotype, secreting very high levels of transforming growth factor-β1 to maintain the activated phenotype, but supporting less tumor formation and invasion. This study also shows that CAFs heterogeneity and the co-operation between different subsets of CAFs are important factors for tumor promotion in OSCC.
2. Role of integrin α11 in progression of OSCC. The work showed that integrin α11 was overexpressed in the stroma of head and neck cancer compared with normal mucosa and correlated positively with the expression of α-SMA. Using an animal model of chemically induced oral carcinogenesis, the group also showed an important role for α11 in the transition from a hyper-proliferative stage to a malignant, invasive stage. Other experiments also showed that α11 expressed by the fibroblasts in the tumor stroma plays a biological role for tumor progression both by directly affecting the invasive properties of oral cancer cells and by providing a pro-angiogenesis microenvironment.
Collaboration between the Oral Cancer Group and the Matrix Biology Group. Research project: Role of integrin α11 in oral carcinogenesis.
PhD thesis: Role of integrin α11 in oral carcinogenesis. In vitro and in vivo studies. Himalaya Parajuli, 2016, ISBN: 978-82-308-3342-1
Plans for the future
Ongoing and further work will focus on combining identification of biomarkers in both the epithelial and stromal compartments, including the inflammatory infiltrate and blood- and lymph vessels, in a comprehensive analysis towards a malignancy index that can be used as a diagnostic and predicitive tool for oral cancer.
In 2015, the Oral Cancer Group started planning a common research project between the Gynaecological Cancer Group and the Oral Cancer Group. A PhD position was allocated for the project. Due to the sudden loss of the PI of the group, Helga Salvesen, the project has been delayed, and focus switched from comparing oral and cervical cancers to comparing oral and vulva cancers.
2016 Spring Interview
Professor Johannessen is the leader of the Bergen Oral Cancer Research Group, BOCG. The group aims to identify key molecules for oral cancer development.
Your group focuses on oral cancer, could you tell us about your findings so far?
"Oral cancer originates from the surface of the oral mucosa, infiltrating the connective tissue and bone, and thereby leading to destructions of the face, if left untreated. Our research group has focused on the interaction between infiltrating epithelial tumor cells and the host cells in the connective tissue, especially the fibroblasts. We have shown that fibroblasts associated with cancer cells (CAFs) play a crucial role in cancer progression and have characterized at the molecular level how CAFs are actively involved in cancer development and invasion. The group has also identified diagnostic biomarkers implicated in the regulation of cell cycle, genomic stability, chromatin maintenance and stem cell regulation and developed a cancer index system of diagnostic and prognostic value based on this panel of molecular markers."
How do you work in your research?
"We have developed a 3D cell culture model mimicking oral mucosa, with surface epithelium and connective tissue, making it possible to study the interaction between these two compartments. This model has been used to compare growth of normal and malignant mucosa. By manipulating the model, e.g. by changing the growth conditions or by exposing the surface to external factors, we have been able to characterize stepwise tumor progression and regulating factors important for tumor infiltration. We are also using advanced animal models in our research, in addition to patient material from oral cancer. This material is achieved from Norwegian patients, but also from the United Kingdom, India, Nepal and Sudan, in close collaboration with researchers from these countries, opening up for comparative studies on oral cancer from different parts of the world."
What is the ultimate goal of your research?
"There is a need for a simple clinical tool that can select premalignant and malignant lesions in the oral cavity. Today there is no diagnostic tool that can predict which white or red oral pre-cancer lesions that will progress to infiltrative oral cancers. Our goal is to develop such a diagnostic and prognostic tool that can stratify patients with oral lesions for more individualized therapy."
Find Johannessen's PubMed publications here.