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The pleiotropic roles of ADAM9 in the biology of solid tumors

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Abstract

A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, proliferation, and cell–cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation. In each of these tumors, ADAM9 may contribute to tumor biology via proteolytic or non-proteolytic mechanisms. For example, in liver cancer, ADAM9 has been found to shed MHC class I polypeptide-related sequence A, contributing towards the evasion of tumor immunity. ADAM9 may also contribute to tumor biology in non-proteolytic ways probably through interaction with different integrins. For example, in melanoma, the interaction between ADAM9 and β1 integrins facilitates tumor stroma cross talks, which then promotes invasion and metastasis via the activation of MMP1 and MMP2. In breast cancer, the interaction between β1 integrins on endothelial cells and ADAM9 on tumor cells facilitate tumor cell extravasation and invasion to distant sites. This review summarizes the present knowledge on ADAM9 in solid cancers, and the different mechanisms which it employ to drive tumor progression.

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Abbreviations

ADAM9:

Disintegrin and metalloproteinase domain-containing protein 9

MHC:

Major histocompatibility complex

MMP1:

Matrix metalloprotease 1

MMP2:

Matrix metalloprotease 2

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Funding

OS acknowledges support by Deutsche Forschungsgemeinschaft (SCHI 871/5, SCHI 871/8, SCHI 871/9, SCHI 871/11, INST 39/900-1, and SFB850-Project Z1), the Excellence Initiative of the German Federal and State Governments (EXC 294, BIOSS), the European Research Council (PoC 780730, ProteaseNter), and the German-Israeli Foundation (Grant no. 1444). This study was supported in part by the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School).

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Authors and Affiliations

  1. Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Victor O. Oria, Paul Lopatta & Oliver Schilling

  2. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany

    Victor O. Oria

  3. Faculty of Biology, University of Freiburg, Freiburg, Germany

    Victor O. Oria

  4. BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany

    Oliver Schilling

  5. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Oliver Schilling

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  1. Victor O. Oria
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Correspondence to Oliver Schilling.

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Oria, V.O., Lopatta, P. & Schilling, O. The pleiotropic roles of ADAM9 in the biology of solid tumors. Cell. Mol. Life Sci. 75, 2291–2301 (2018). https://doi.org/10.1007/s00018-018-2796-x

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