Daniela Elena Costea
Professor Daniela Elena Costea and her team in the Experimental Pathology Research Group are focusing on characterizing the interactions between epithelial (stem) cells and their microenvironment in normal conditions and during carcinogenesis.
Understanding the role of epithelial-microenvironment interactions in carcinoma progression.
• Epithelial-mesenchymal interactions in oral and vulvar squamous cell carcinoma.
Professor Costea's team has revealed several aspects of the epithelial-mesenchymal interactions in head and neck cancers. Now they are focusing on the epithelial-mesenchymal interactions in terms of energy exchange. Particularly, they are interested in the differences in the energy metabolism and epithelial-mesenchymal interactions between HPV negative and HPV positive cancer cells and surrounding fibroblasts in two cancers that share HPV as a common etiological agent: head and neck and vulvar squamous cell carcinoma. Common pathognomonic pathways have been already identified for oral and vulvar squamous cell carcinoma. This project is aiming to develop 3D models of HPV+ and HPV- oral and vulvar cancer and to reveal and target common pathological pathways leading to carcinogenesis in oral and vulva & vagina.This project includes a CCBIO collaboration with Associate Investigator Line Bjørge.
• Exploring the use of electronic nose for diagnosis of head and neck premalignant and malignant lesions in populations with different demographical and etiological background.
Breathomic is a new, non-invasive method for disease detection based on specific patterns of volatile organic compounds present in the exhaled air. Due to its low costs and simple logistics, this method holds the promise for being developed into a tool for disease screening in developing countries. Costea's aim is to determine if electronic nose modules with a patented on-board temperature control can be used for detection of oral cancer in the settings of Sudan, a developing country where oral cancer poses a major burden of disease. For this the team uses an e-nose device developed by the Aenose Company, the Netherlands.
Project 1: Pairs of normal and cancer cells and associated fibroblasts from oral and vulvar cancer have been isolated and used to establish 3D models of HPV+ and HPV- of oral and vulva cancer. To our knowledge, these are the first 3D models of human vulva cancer. Using 2D and 3D co-culture models, the team could show that oral cancer cells induce a “reverse Warburg effect” in normal fibroblasts by promoting mitochondrial dysfunction and oxidative stress in different ways that fuel ATP production in cancer cells.
Project 2: AA specific breath volatile organic compounds pattern for Sudanese patients has been developed. The e-nose technique was able to discriminate between oral cancer patients and healthy controls in the hospital settings of Sudan (81% accuracy).
Project 1: To develop specific vectors for clinical trials targeted towards the key molecules identified in this study to play a crucial role in epithelial-mesenchymal interactions.
Project 2: The use of electronic nose method is currently further tested on a larger scale for use as a screening tool for detection of HNC.
Current challenges in the field
Head and neck cancer is a very heterogeneous disease with a high tumor mutation burden. Nevertheless, these mutations are not drivers but rather random mutations and thus, although it is expected that being tumors with high mutation rate head and neck tumors should respond better to novel pharmaceutical treatment, the response rate so far is quite disappointing. This is also partly due to inappropriate preclinical models that use rodents as preclinical surrogates for human cancer. Therefore Professor Costea is directing the team's efforts for establishing human 3D models for cancers and using them for modulating tumor progression by targeting epithelail-mesenchymal intercations and the tumor microenvironment as a whole rather that tumor cells alone.