ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins
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ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins. / Mygind, Kasper J.; Nikodemus, Denise; Gnosa, Sebastian; Kweder, Ramya; Albrechtsen, Nicolai J.Wewer; Kveiborg, Marie; Erler, Janine T.; Albrechtsen, Reidar.
In: International Journal of Molecular Sciences, Vol. 25, No. 11, 5871, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - ADAM12-Generated Basigin Ectodomain Binds β1 Integrin and Enhances the Expression of Cancer-Related Extracellular Matrix Proteins
AU - Mygind, Kasper J.
AU - Nikodemus, Denise
AU - Gnosa, Sebastian
AU - Kweder, Ramya
AU - Albrechtsen, Nicolai J.Wewer
AU - Kveiborg, Marie
AU - Erler, Janine T.
AU - Albrechtsen, Reidar
N1 - Publisher Copyright: © 2024 by the authors.
PY - 2024
Y1 - 2024
N2 - 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 in exosomes 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.
AB - 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 in exosomes 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.
KW - CD147/Basigin
KW - disintegrin and metalloproteinase
KW - extracellular matrix
U2 - 10.3390/ijms25115871
DO - 10.3390/ijms25115871
M3 - Journal article
C2 - 38892056
AN - SCOPUS:85195847476
VL - 25
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 11
M1 - 5871
ER -
ID: 395581699