Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma

Abstract Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early...

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Autores principales:	Jasper C. Lee, Demitra M. Yotis, Ji Yun Lee, Marie A. Sarabusky, Bradly Shrum, Audrey Champagne, Ola Z. Ismail, Elena Tutunea-Fatan, Hon S. Leong, Lakshman Gunaratnam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3782d411acd84457baceedd045480f73
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spelling	oai:doaj.org-article:3782d411acd84457baceedd045480f732021-12-02T15:03:05ZKidney injury molecule-1 inhibits metastasis of renal cell carcinoma10.1038/s41598-021-90919-82045-2322https://doaj.org/article/3782d411acd84457baceedd045480f732021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90919-8https://doaj.org/toc/2045-2322Abstract Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early detection of RCC, but its pathophysiological significance in RCC remains unclear. We generated human and murine RCC cell lines either expressing or lacking KIM-1, respectively, and compared their growth and metastatic properties using validated methods. Surprisingly, KIM-1 expression had no effect on cell proliferation or subcutaneous tumour growth in immune deficient (Rag1−/−) Balb/c mice, but inhibited cell invasion and formation of lung metastasis in the same model. Further, we show that the inhibitory effect of KIM-1 on metastases was observed in both immune deficient and immune competent mice. Transcriptomic profiling identified the mRNA for the pro-metastatic GTPase, Rab27b, to be downregulated significantly in KIM-1 expressing human and murine RCC cells. Finally, analysis of The Cancer Genome Atlas (TCGA) data revealed that elevated HAVCR1 mRNA expression in the two most common types of RCC, clear cell and papillary RCC, tumours correlated with significantly improved overall patient survival. Our findings reveal a novel role for KIM-1 in inhibiting metastasis of RCC and suggests that tumour-associated KIM-1 expression may be a favourable prognostic factor.Jasper C. LeeDemitra M. YotisJi Yun LeeMarie A. SarabuskyBradly ShrumAudrey ChampagneOla Z. IsmailElena Tutunea-FatanHon S. LeongLakshman GunaratnamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jasper C. Lee Demitra M. Yotis Ji Yun Lee Marie A. Sarabusky Bradly Shrum Audrey Champagne Ola Z. Ismail Elena Tutunea-Fatan Hon S. Leong Lakshman Gunaratnam Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
description	Abstract Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early detection of RCC, but its pathophysiological significance in RCC remains unclear. We generated human and murine RCC cell lines either expressing or lacking KIM-1, respectively, and compared their growth and metastatic properties using validated methods. Surprisingly, KIM-1 expression had no effect on cell proliferation or subcutaneous tumour growth in immune deficient (Rag1−/−) Balb/c mice, but inhibited cell invasion and formation of lung metastasis in the same model. Further, we show that the inhibitory effect of KIM-1 on metastases was observed in both immune deficient and immune competent mice. Transcriptomic profiling identified the mRNA for the pro-metastatic GTPase, Rab27b, to be downregulated significantly in KIM-1 expressing human and murine RCC cells. Finally, analysis of The Cancer Genome Atlas (TCGA) data revealed that elevated HAVCR1 mRNA expression in the two most common types of RCC, clear cell and papillary RCC, tumours correlated with significantly improved overall patient survival. Our findings reveal a novel role for KIM-1 in inhibiting metastasis of RCC and suggests that tumour-associated KIM-1 expression may be a favourable prognostic factor.
format	article
author	Jasper C. Lee Demitra M. Yotis Ji Yun Lee Marie A. Sarabusky Bradly Shrum Audrey Champagne Ola Z. Ismail Elena Tutunea-Fatan Hon S. Leong Lakshman Gunaratnam
author_facet	Jasper C. Lee Demitra M. Yotis Ji Yun Lee Marie A. Sarabusky Bradly Shrum Audrey Champagne Ola Z. Ismail Elena Tutunea-Fatan Hon S. Leong Lakshman Gunaratnam
author_sort	Jasper C. Lee
title	Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
title_short	Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
title_full	Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
title_fullStr	Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
title_full_unstemmed	Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
title_sort	kidney injury molecule-1 inhibits metastasis of renal cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3782d411acd84457baceedd045480f73
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Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma

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