Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Gunaratnam, Lakshman

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.

Summary for Lay Audience

Metastasis is often the deadliest aspect of cancer, and is characterized by the secondary spread of cancer cells to distant sites of the body from the primary tumour. Over a third of patients with renal cell carcinoma (RCC) - the most common form of kidney cancer - present with metastases at the time of diagnosis. Kidney injury molecule 1 (KIM-1) is a cell-surface protein expressed by >90% of RCC tumours. Preliminary data from our lab indicates that KIM-1 overexpression predicts overall survival in patients. Here we sought to determine if tumour KIM-1 plays a role in RCC metastasis to the lungs - the most common site of metastasis in RCC. The metastatic potential of KIM-1-expressing cells was investigated, and the differences in gene expression between KIM-1+ and KIM-1neg cells were analyzed.

We concluded that KIM-1 inhibits RCC invasion and metastasis to the lungs, indepent of the adaptive immune system. RNA-sequencing analysis of the genes provided putative downstream effectors of KIM-1.

Available for download on Monday, August 31, 2020

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