ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins - Abstract

Sep 21, 2026

Uploaded by Hazel

Desmoplasia is a hallmark of aggressive cancers driven by coordinated protein production and degradation. Basigin (CD147) is a type 1 integral membrane receptor secreted in exosomes or released by ectodomain shedding. This study examines how an ADAM12-generated basigin ectodomain supports cancer progression. Results show recombinant ectodomain binding to β1 integrin, promoting gelatin degradation and cancer cell migration through MMP- and β1-integrin-dependent mechanisms.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Basigin and desmoplasia in aggressive cancer

ADAM12-generated ectodomain mechanism

Effects on extracellular matrix proteins

Feedback loop model

Article ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins Kasper J. Mygind 1, Denise Nikodemus 1, Sebastian Gnosa 1, Ramya Kweder 1, Nicolai J. Wewer Albrechtsen 2, Marie Kveiborg 1, Janine T. Erler 1 and Reidar Albrechtsen 1, * Citation: Mygind, K.J.; Nikodemus, D.; Gnosa, S.; Kweder, R.; Albrechtsen, N.J.W.; Kveiborg, M.; Erler, J.T.; Albrechtsen, R. ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins. Int. J. Mol. Sci. 2024, 25, 5871 . [https://doi.org/10.3390/ijms25115871](https://doi.org/10.3390/ijms25115871) [Academic Editor: Zolt](Academic Editor: Zolt)án Wiener Received: 21 March 2024 Revised: 15 May 2024 Accepted: 25 May 2024 Published: 28 May 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; [kmygind@sund.ku.dk](kmygind@sund.ku.dk) (K.J.M.); denise.nikodemus@biologie.uni-freiburg.de (D.N.); [seg@minervaimaging.com](seg@minervaimaging.com) (S.G.); [ramya.kweder@sund.ku.dk](ramya.kweder@sund.ku.dk) (R.K.); [marie.kveiborg@sund.ku.dk](marie.kveiborg@sund.ku.dk) (M.K.); [janine.erler@bric.ku.dk](janine.erler@bric.ku.dk) (J.T.E.) 2 Department of Clinical Biochemistry, Copenhagen University Hospital-Bispebjerg, 2400 Copenhagen, Denmark; [nicolai.albrechtsen@regionh.dk](nicolai.albrechtsen@regionh.dk) * Correspondence: [reidaral@sund.ku.dk](reidaral@sund.ku.dk) Abstract: Desmoplasia is a common feature of aggressive cancers, driven by a complex interplay of protein production and degradation. Basigin is a type 1 integral membrane receptor secreted inexosomes or released by ectodomain shedding from the cell surface. Given that soluble basigin is increased in the circulation of patients with a poor cancer prognosis, we explored the putative role of the ADAM12-generated basigin ectodomain in cancer progression. We show that recombinant basigin ectodomain binds β1 integrin and stimulates gelatin degradation and the migration of cancer cells in a matrix metalloproteinase (MMP)-and β1-integrin-dependent manner. Subsequent in vitro and in vivo experiments demonstrated the altered expression of extracellular matrix proteins, including fibronectin and collagen type 5 . Thus, we found increased deposits of collagen type 5 in the stroma of nude mice tumors of the human tumor cell line MCF7 expressing ADAM12—mimicking the desmoplastic response seen in human cancer. Our findings indicate a feedback loop between ADAM12 expression, basigin shedding, TGFβ signaling, and extracellular matrix (ECM) remodeling, which could be a mechanism by which ADAM12-generated basigin ectodomain contributes to the regulation of desmoplasia, a key feature in human cancer progression. Keywords: CD147/Basigin; disintegrin and metalloproteinase; extracellular matrix 1. Introduction The extracellular matrix metalloproteinase inducer (EMMPRIN), also termed CD147/ basigin, is a glycoprotein belonging to the immunoglobulin family [1,2] . Four variants (basigin 1–4) exist, but the most abundant and well-studied is isoform 2 (henceforth termed basigin) . Basigin (BSG) is a 269 amino acid long type I transmembrane protein composed of an N-terminal signal sequence, a 186 residue-long extracellular portion consisting of two Ig-like domains (D1 and D2), a transmembrane domain, and a C-terminal cytoplasmic domain [3] . It has been shown to exert several different functions at the plasma membrane, acting as a homo-or heterodimer in eith

FAQs

What is the role of basigin in aggressive cancer biology?

Basigin is a type 1 integral membrane receptor that can be released via exosomes or ectodomain shedding. Elevated soluble basigin is linked to poor cancer prognosis and relates to cancer progression processes such as invasion.

How does the ADAM12-generated basigin ectodomain influence cancer cell behavior?

The recombinant ADAM12-generated basigin ectodomain binds β1 integrin and stimulates gelatin degradation and cancer cell migration. The effects occur in an MMP- and β1-integrin-dependent manner.

What extracellular matrix changes were observed in vitro and in vivo?

In vitro and in vivo experiments showed altered expression of extracellular matrix proteins, including fibronectin and collagen type 5. Tumors in nude mice bearing ADAM12-expressing MCF7 cells showed increased collagen type 5 deposits, mimicking desmoplasia-like stromal response.

Sep 21, 2026

Uploaded by Hazel