Engineered Endometrial Clear Cell Cancer-on-a-Chip Reveals Early Invasion-Metastasis Cascade of Cancer Cells.

Abstract

Endometrial clear cell cancer (ECCC) is an extremely rare and highly malignant subtype of endometrial cancer. For most ECCC patients, cancer metastasis is the major cause of death. To date, due to the complexity of cancer evolution and the small number of cases, the metastasis of ECCC at the early stage remains largely unknown. Herein, we modeled the early invasion-metastasis cascade of ECCC by coculturing the ECCC patient-derived tumor cells (PDTCs) and primary human vascular endothelial cells on a microfluidic chip. With the chip, we for the first time replicated the dynamic migration of PDTCs into the surrounding stroma, including the intravasation and extravasation of PDTCs through the capillaries/microvessels, and presented the changes in the morphology and permeability of capillaries, with the decreased diameter and the increased permeability after cancer metastasis. We found that PDTCs were more invasive than the common endometrial adenocarcinoma cells. In addition, we preliminarily explored the inhibition of drugs on the early PDTC infiltration. This study provides new ideas for better understanding of ECCC evolution.