ADAMTS1 protease is required for a balanced immune cell repertoire and tumour inflammatory response

Scientific Reports
Francisco Javier Rodríguez-BaenaJuan Carlos Rodríguez-Manzaneque

Abstract

Recent advances have emphasized the relevance of studying the extracellular microenvironment given its main contribution to tissue homeostasis and disease. Within this complex scenario, we have studied the extracellular protease ADAMTS1 (a disintegrin and metalloprotease with thrombospondin motif 1), implicated in vascularization and development, with reported anti- and pro-tumorigenic activities. In this work we performed a detailed study of the vasculature and substrates in adult organs of wild type and Adamts1-deficient mice. In addition to the expected alterations of organs like kidney, heart and aorta, we found that the lack of ADAMTS1 differently affects lymphocyte and myeloid populations in the spleen and bone marrow. The study of the substrate versican also revealed its alteration in the absence of the protease. With such premises, we challenged our mice with subcutaneous B16F1 syngeneic tumours and closely evaluated the immune repertoire in the tumours but also in the distant spleen and bone marrow. Our results confirmed a pro-inflammatory landscape in the absence of ADAMTS1, correlating with tumour blockade, supporting its novel role as a modulator of the immune cell response.

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Citations

Nov 15, 2020·Cancers·Alex Gordon-Weeks, Arseniy E Yuzhalin
Mar 16, 2021·Matrix Biology Plus·Silvia Redondo-GarcíaJuan Carlos Rodríguez-Manzaneque
Oct 5, 2021·General and Comparative Endocrinology·Yong Zhu

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Methods Mentioned

BETA
flow cytometry
biopsies
FCS
FACS

Software Mentioned

GraphPad Prism
Image J
DIVA
GraphPad

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