Figure 2: Establishment of Vascularized Micro-Tumors (VMTs).

(a) Time course of HCT116 growth in the VMT. Lentivirally-transduced HCT116 (green) and EC (red) were visualized by confocal microscopy. Stromal/perivascular cells were unlabeled. (Scale bar 100 μm). (b) The VMT platform supports growth of multiple tumor cell types, including additional CRC (SW620, SW480), breast cancer (MCF-7) and melanoma (MNT-1). Images were taken between days 10 and 12. (c,d) Time course of HCT116 (green) response to FOLFOX (10 μM Folinic acid (leucovorin), 100 μM 5-FU, and 5 μM Oxaliplatin) in the VMT. Data are shown relative to t = 0, which is time of first exposure to drug (usually 6–8 days after initiation of culture). Cells were also monitored for 96 h after drug removal. Error bars show mean ± s.d of 3 replicates (n = 2) (p < 0.05 control vs treated FOLFOX). (Scale bar 50 μm). (e) Dose-response of Oxaliplatin on HCT116 cells. VMTs or cells growing in 2D were exposed to drug for 48 h, and tumor cell number and viability were assessed by fluorescence intensity measurement or XTT assay. Data are normalized to time zero of drug exposure and shown as percentage of control. Error bars show mean ± s.d (n = 3) (p < 0.05, 2D vs VMT). (f,g) Time course of MDA-MB-231 cells exposed to Taxol (100 nM). Data are normalized to first day of drug exposure. Error bars show mean ± s.d of 3 replicates (p < 0.05 control vs treated Taxol). (h) Differential effects of anti-tumor drugs on the breast cancer cell lines MCF-7 (ERα+) and MDA-MB-231 (triple-negative). VMTs were first exposed to E2/drugs between days 6 and 8 and cultured for an additional 96 h. Drugs were removed from the media at 48 h. Data are normalized to first day of drug exposure and are shown as percentage of control. Error bars show mean ± s.d (n = 2–4) (*p < 0.05 vs control; ^§p < 0.05 MCF-7 vs MDA-MB-231).