Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hyperactive Neutrophils Infiltrate Vital Organs of Tumor Bearing Host and Contribute to Gradual Systemic Deterioration With Tumor Progression

Version 1 : Received: 1 September 2021 / Approved: 2 September 2021 / Online: 2 September 2021 (12:20:02 CEST)

How to cite: Rawat, K.; Syeda, S.; Shrivastava, A. Hyperactive Neutrophils Infiltrate Vital Organs of Tumor Bearing Host and Contribute to Gradual Systemic Deterioration With Tumor Progression. Preprints 2021, 2021090039 (doi: 10.20944/preprints202109.0039.v1). Rawat, K.; Syeda, S.; Shrivastava, A. Hyperactive Neutrophils Infiltrate Vital Organs of Tumor Bearing Host and Contribute to Gradual Systemic Deterioration With Tumor Progression. Preprints 2021, 2021090039 (doi: 10.20944/preprints202109.0039.v1).

Abstract

Various studies have addressed the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, cancer has a systemic impact which targets various organs thus challenging the overall physiology of the host. So, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern the systemic role of neutrophils, we monitored their number and function at different stages of tumor growth in Dalton’s lymphoma mice model. Notably, we observed a gradual increase in neutrophil count in blood and their infiltration in vital organs of tumor bearing mice. In parallel, we observed damaged histoarchitecture with significant alterations in biochemical parameters that aggravated with tumor progression. We next examined systemic impact of neutrophil by assessing neutrophil elastase, myeloperoxidase, and matrix metalloproteinases (MMP-8 and MMP-9) wherein we found their upregulated expression and activity in tumor condition. Taken together, our results demonstrate high infiltration and hyperactivation of neutrophils which possibly account for gradual systemic deterioration during cancer progression. Our findings thus implicate neutrophils as a potential therapeutic target that may help to reduce the overall fatality rate of cancer.

Keywords

Neutrophils; systemic deterioration; hyperactivation; neutrophil elastase; matrix metalloproteinases; myeloperoxidase

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