Prostate cancer is the most common cancer in males and a major cause of cancer-related morbidity and mortality in men. Current treatments of prostate cancer with androgen deprivation therapy are initially very effective. Beneficial responses, however, are followed by tumour recurrence at distant sites leading to incurable metastatic castration-resistant disease (mCRPC) including cancer-induced bone disease. Upon bone colonisation, prostate cancer cells alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteo-induction). This, in turn, may eventually cause considerable morbidity with bone pain, nerve compression syndromes, pathologic fractures, and myelophthesic anaemia (myelophthisis), i.e. the displacement of hematopoietic bone-marrow by expanding bone metastatic prostate cancer tissue.
In this presentation, mechanism of osteotropism of prostate cancer will be discussed in the context of multiple tumour-stroma interactions, encompassing cell-cell and cell-matrix interactions. Our studies shown that the subpopulation of cancer stem/progenitor cells play a key role in successful bone/bone marrow colonisation. Moreover, we have identified bone marrow/bone-specific stroma response to prostate cancer-induced osteoblastic bone metastasis. A robust induction of gene expression involved in osteogenesis and angiogenesis dominates the osteoblastic bone marrow stromal transcriptome. Strikingly, this translates in an amplification of hematopoietic and prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteo-inductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with haematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.
Prof. Gabri van der Pluijm is a Graduate in Biology with a PhD in Bone Biology from the University of Leiden. After a visting fellow position at the National Institutes of Health (Bethesda, MD, USA) and a senior researcher position at the Leiden University Medical Center, he was appointed as associate professor at the department of Urology and is heading the Urological oncology Research Laboratory. His group developed ‘near-patient’ disease models that are exploited for functional studies, biomedical imaging and drug development studies for prostate, bladder and breast cancer.
Current research -with funding from the EU and national cancer research programmes- is focused on 1. identification of pathophysiological mechanisms of tumour progression and therapy resistance (chemotherapy and castration resistance), 2. development of new, tumour-targeted therapy for urological malignancies (drug development, nanodrug delivery, drug repositioning/repurposing, immunotherapy of cancer) and 3) development and validation of new imaging agents for applied medical imaging of urological malignancies.
He is a board member the European Association for Urology(EAU) (EAU Section Urology Research/ESUR), member of various (inter)national grant review boards, reviewer for multiple international scientific journals, invited/guest lecturer, tutor for medical and biomedical students, member of the Study Programme Committee for Biomedical Sciences at Leiden University, mentor for several PhD students/postdocs. He has served as a co-promotor/external examinator on different national and international PhD (guidance) committees. #publications > 135 original articles. H-index >45.