磁性粒子を使った細胞工学?細胞機能評価ヘの応用?

摘要

In vitro three-dimensional (3D) cancer models were developed to observe the invasive capacity of melanoma cell spheroids co-cultured with a vascular-formed endothelial cell network. An array-like multicellular pattern of mouse melanoma cell line B16F1 was developed by magnetic cell labeling using a pin-holder device to allocate magnetic force. When the B16F1 was patterned together with a vascular network of human umbilical vein epithelial cells (HUVECs), spreading and progression were observed along the HUVEC network. B16F1 cells more than 80 mm away from HUVECs remained in a compact spheroid shape, while the B16F1 in the proximity of HUVECs aggressively changed their morphology and migrated. The mRNA expression levels of IL-6, MDR-1, and MMP-9 in the B16F1 increased along with their distance in the HUVEC network, and these expressions were increased 5-,3-, and 2-fold in the B16F1 close to HUVEC (within 80 mm) as compared to that far from HUVEC (further than 80 mm). Our results clearly show that malignancy of tumor cells was enhanced in proximity to vascular endothelial cells and also led to intravasation.