Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Potential Role of Cathepsin K in Regulation of Micro Tumor Environment, Onset and Progression of Cancers in Human- A Review

Version 1 : Received: 25 March 2020 / Approved: 27 March 2020 / Online: 27 March 2020 (10:33:50 CET)

How to cite: Cooray, R.; Madubashetha, H.; Wickramasinghe, S.; Warnakula, L.; De Silva, N. Potential Role of Cathepsin K in Regulation of Micro Tumor Environment, Onset and Progression of Cancers in Human- A Review. Preprints 2020, 2020030405 (doi: 10.20944/preprints202003.0405.v1). Cooray, R.; Madubashetha, H.; Wickramasinghe, S.; Warnakula, L.; De Silva, N. Potential Role of Cathepsin K in Regulation of Micro Tumor Environment, Onset and Progression of Cancers in Human- A Review. Preprints 2020, 2020030405 (doi: 10.20944/preprints202003.0405.v1).

Abstract

The effect of proteolytic enzymes including Cathepsin K, a cysteine cathepsin, in onset and progression of cancers in human has been research intensive. Cathepsin K involves in many aspects and stages of cancers including apoptosis, cell proliferation, cancer immunology, inflammatory cell recruitment to tumors and aiding in the process of mobilization of normal healthy cells from their tissue compartments assisting in metastasis and angiogenesis. The objective of this review is to collect together and summarize and analyze the biochemical and physiological pathways of how cathepsin K is involved in onset and progression of cancers with more emphasis on breast and prostate cancers and cathepsin K regulated mechanisms underlying metastasis of such cancers to bones. Information for the review was gathered through published literature from global databases such as Google Scholar, PUBMED and NCBI on different studies on physiological interactions between enzymatic activity of cathepsin K with cancers and metastasis to bones. Analysis of published studies reveal that immunohistochemical studies of breast cancer cells indicate that they overexpress cathepsin K resulting in induction of aberrant mechanisms of cell signaling in breast cancers, creating a higher tendency for their metastasis to bones. Immunohistochemical, immunoprecipitation and fluorgenic assays of several studies done on the association of the same enzymatic activity on prostate cancers shows elevated levels of cathepsin K. Lesions derived from prostate cancer cell masses were observed to undergo increased bone formation and resorption levels. Such resorption levels cause secretion of biological factors promoting tumor expansion. In addition, studies indicate that Cathepsin K was observed to be a key component promoting higher bone resorption levels in patients suffering from cancer. Authors suggest that, to completely understand the association of cathepsin K on cancerous cells and their mechanism in metastasis, distributary patterns of cathepsin K in healthy human tissues needs to be extensively studied initially. It is also suggested that metastasis of breast and prostate cancers to bone could be terminated and overcome by successful production of efficient and precise inhibitory therapeutics targeting the enzymatic activity of Cathepsin K with minimum unintended adverse health effects.

Subject Areas

cancer; Cathepsin K; human; metastasis; physiology

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