Modulation of tumor-microenvironmental factors and cancer growth in co-cultures of fresh human lung tissue and patient-derived cancer cells

Formation of metastases marks the main cause of death in cancer and is characterized by complex processes, which can only partly be reflected in most in-vitro models due to a lacking human microenvironment. Cisplatin, bevacizumab and vemurafenib were used to modulate different aspects of tumorigenesis in co-cultures of patient-derived, disseminated melanoma cells or MDA-MB-231 cells and fresh human lung tissue as well as fresh human tumor tissue slices. Neoangiogenetic biomarker VEGF was elevated 3.5fold in co-cultures and 5.4fold in lung tumor slices after 48h. Treatment with bevacizumab [200 mg/mL] suppressed VEGF-release 24fold in co-cultures and 25fold in lung tumor tissue slices after 48h, also leading to impaired endothelial cell migration of the supernatants (81% in co-cultures, 83% in tumor slices). Cisplatin treatment [50mM] led to a decline of viability in co-cultures by up to 37.5% and in tumor slices up to 48.7% after 72h. Co-cultures and tumor slices were less sensitive in regards to their respective anti-cancer drug efficacy than the 2D culture. To address patient-specific genetic disparities, co-cultures with disseminated melanoma cells were performed with both patient-derived cells carrying BRAF mutation V600E and non-mutated cells. Treatment with vemurafenib reduced V600E cancer cell number (IC50=6µM) after 48 hours while non-mutated cells showed no significant cancer cell decrease. Here we show that tumor cells in solid tumors and seeded into healthy lung tissue are sensitive to tumor treatments ex vivo. This work aims to translate cancer drug efficacy data from animals towards humans to optimize clinical trial outcome.