The role of kidney injury molecule-1 in the metastasis of renal cell carcinoma
Abstract
Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by >90% of RCC tumours. Preliminary data mined from The Cancer Genome Atlas RNA-sequencing database indicates that KIM-1 overexpression predicts overall survival in patients. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to the lungs. In vitro invasion and in vivo metastasis assays were performed to investigate the metastatic potential of KIM-1-expressing cells, and RNA-seq was conducted to identify differentially expressed genes between KIM-1+ and KIM-1neg cells.
Invasion was significantly decreased in vitro in both murine and human RCC cells that expressed KIM-1. We concluded that KIM-1 inhibits RCC extravasation and metastasis to the lungs, independent of adaptive immunity. RNA-seq analysis provided putative downstream effectors of KIM-1.