The role of microRNAs in Homing and Seeding of Prostate Cancer Metastases in Bone.
The focus of the project will be the miRNA regulation in prostate cancer and the role of extracellular vesicle miRNAs in cellular communication enabling homing and establishment to metastatic sites and the prognostic and therapeutic potential.
Prostate cancer is the most common cancer in men in industrialized countries, and the manifestation of distant metastasis is the major cause of cancer-related deaths in these men. The overall aim of this project is to increase the understanding of cancer metastasis in order to address the unmet clinical need for novel therapeutic strategies targeting metastatic prostate cancer. The development of metastases is a complex, dynamic and inefficient process, involving detachment of the tumour cells from the primary site, entering and surviving in the bloodstream, migration to distant locations, extravasation and establishment at distant sites. These steps are dependent on interaction between the tumour cell and the microenvironment and cellular plasticity. Extracellular vesicles containing tumour-derived miRNAs can significantly impact the plasticity of other tumour cells and also effect the cells present in the distant microenvironment priming the metastatic niche as well as subvert the immune cells drive.
The specific aim of this project is to investigate miRNAs contained in extracellular vesicles in homing and seeding of prostate cancer cells in bone environment. The student will study how miRNAs in extracellular vesicles secreted by tumour cells and cells in the bone microenvironment and tumour cells can facilitate priming of the metastatic niche, the metastatic homing, the survival and expansion of tumour cells in the bone environment, and thus contribute to the metastatic process. This will be studied in vitro using reporter systems and functional cell based assays as well as in vivo imaging in mouse models to elucidate the mechanisms of action. All findings will be validated in clinical material. This project aim to increase the understanding of cancer metastasis and as the reversibility of this type of regulation presents a therapeutic interference option, it can lead to improved design of novel therapeutic strategies to target the metastatic spread.