Cancer-associated mutations in the canonical cleavage site do not influence CD99 shedding by the metalloprotease meprin β but alter cell migration in vitro.

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Bedau, Tillmann, Schumacher, Neele, Petersen, Florian, Prox, Johannes, Arnold, Philipp, Koudelka, Tomas, Helm, Ole, Schmidt, Frederike, Rabe, Björn, Jentzsch, Marlene, Rosenstiel, Philip, Sebens, Susanne, Tholey, Andreas, Rose-John, Stefan and Becker-Pauly, Christoph (2017) Cancer-associated mutations in the canonical cleavage site do not influence CD99 shedding by the metalloprotease meprin β but alter cell migration in vitro. Oncotarget, 8 . DOI 10.18632/oncotarget.18966.

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Supplementary data:

Abstract

Transendothelial cell migration (TEM) is crucial for inflammation and metastasis. The adhesion molecule CD99 was shown to be important for correct immune cell extravasation and is highly expressed on certain cancer cells. Recently, we demonstrated that ectodomain shedding of CD99 by the metalloprotease meprin β promotes TEM in vitro. In this study, we employed an acute inflammation model (air pouch/carrageenan) and found significantly less infiltrated cells in meprin β knock-out animals validating the previously observed pro-inflammatory activity. To further analyze the impact of meprin β on CD99 shedding with regard to cell adhesion and proliferation we characterized two lung cancer associated CD99 variants (D92H, D92Y), carrying point mutations at the main cleavage site. Interestingly, ectodomain shedding of these variants by meprin β was still detectable. However the cleavage site shifted to adjacent positions. Nevertheless, expression of CD99 variants D92H and D92Y revealed partial misfolding and proteasomal degradation. A previously observed influence of CD99 on Src activation and increased proliferation could not be confirmed in this study, independent of wild-type CD99 or the variants D92H and D92Y. However, we identified meprin β as a potent inducer of Src phosphorylation. Importantly, we found significantly increased cell migration when expressing the cancer-associated CD99 variant D92H compared to the wild-type protein.

Document Type: Article
Keywords: CD99; inflammation; lung cancer; meprin β; proteolytic shedding
Research affiliation: Kiel University
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
Open Access Journal?: Yes
Publisher: Impact Journals
Projects: Future Ocean
Date Deposited: 08 Jan 2018 11:06
Last Modified: 23 Sep 2019 22:21
URI: https://oceanrep.geomar.de/id/eprint/41253

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