Effect on Invasive Capacity of Cancer Cell Spheroid Co-Cultured with Vascular Endothelial Cell Network Using In Vitro 3D Patterning Model

Yamamoto, Shuhei ;   Okochi, Mina ;   Honda, Hiroyuki

In vitro three dimensional (3D) cancer models were developed to observe the invasive capacity of cancer cell spheroids co-cultured with the vascular network-formed human umbilical vein endothelial cell (HUVEC). An array-like multicellular pattern of highly metastatic mouse melanoma cell line B16F1 was developed by magnetic cell labeling using a pin-holder device and magnetic force. When the B16F1 patterned together with HUVEC network, the B16F1 cells within 80 µm distance of HUVEC showed invasive morphology and migrated along the HUVEC network. The gene expressions of IL-6 and MMP-9 in B16F1 increased along with the distance the HUVEC network, and these expressions were increased by 5 and 2-fold in the B16F1 within 80 µm distance of HUVEC than that over 80 µm distance from HUVEC. Our results clearly show that malignancy of tumor cells is enhanced in proximity to vascular endothelial cells and leads to intravasation.