Metastasis is the leading cause of death for cancer patients. To colonize distant organs, cancer cells communicate with their environment to overcome obstacles such as infiltration of foreign tissues and adaptation to supportive niches. Although metastasis is an inefficient process; we are currently failing to understand it, prevent it and have sustainable answers.

Prof. Olivier De Wever's group from the Laboratory for Experimental Cancer Research devotes its resources to improving the understanding of the communicative determinants between cancer cells and their host tissue. The results of this research can be clustered into two topics:

1) 3D cell culture models (such as spheroids) and patient-derived models (ex vivo) to study metastasis-associated cellular activities. Patient-derived models may preserve the three-dimensional (3D) architecture and tumor microenvironment (TME) of the original tumor, as such integrating more biology into therapeutic decision making by taking other drivers (metabolic, phenotypic, epigenetic and TME) of tumor behavior and evolution during treatment into account. Spheroids, near spherical cellular aggregates, show diffusive nutrient and oxygen supply leading to metabolic gradients from the periphery to the inner core causing spatial heterogeneity in proliferation, quiescence, necrosis and differentiation. Ex vivo tissue fragments are obtained from surgical residual material in collaboration with many surgery groups at UZ-Gent (but also canine patients from faculty of Veterinary Science. Their main advantage is the preservation of the immune cells, fibroblast and matrix architecture as found in the patient. Both spheroids and tissue fragment models are extensively evaluated in the lab for culture conditions, ex vivo evolution by multiple complementary microscopy and omic technologies. Finaly, multiple treatments (radiotherapy, small molecules, immunotherapy and chemotherapy) are evaluated on spheroids and tissue fragments. Their response is intensively investigated and discussed with medical oncologists, radiotherapists etc.

2) The identification of adaptive communication skills between cancer cells and host cells (cancer-associated fibroblasts, CAF) and its impact on cancer management strategies. Cancer-associated fibroblasts (CAF) represent the most prominent stromal cell type in the TME of solid tumors. CAF influence cancer progression through heterotypic cellular, matrix and secretory interactions. CAF plasticity results in a spectrum of different functional states; the best characterized are a myofibroblast and an inflammatory state (myCAF vs iCAF). myCAF accumulate extracellular matrix (ECM) and are contractile through α-smooth muscle actin (SMA) stress fibers; iCAF secrete inflammatory cytokines/chemokines. We investigate the communicative determinants between CAF and cancer cells through functional assays, advanced microscopy settings and multi-omic procedures. We investigate how CAF change their state under influence of cancer cells and during therapy. Reciprocally, we investigate how cancer cells respond to these different CAF states.