title: The disintegrin domain of ADAM17 antagonises fibroblast‑carcinoma cell interactions.
abstract: The malignant phenotype of carcinoma cells depends on their ability to invade into their microenvironment promoting metastasis. Therefore, carcinoma cells overexpress many proteins, including A disintegrin and metalloproteases (ADAMs). ADAM17 is expressed by different cancer cell lines and possesses adhesive as well as enzymatic activities. To address the adhesive properties in tumour progression the recombinantly expressed soluble disintegrin domain of ADAM17 was employed. Fibroblasts and carcinoma cells adhere to the immobilized disintegrin domain. Additionally, the soluble disintegrin domain impaired fibroblast-carcinoma cell interactions and increased the shedding activity of ADAM17. Silencing of ADAM17 in fibroblasts or in carcinoma cells decreases cell-cell interaction between these cells. In summary, our results show that the adhesive properties of ADAM17 are mediated by its disintegrin domain and enables carcinoma cells to interact with their microenvironment.
authors.affiliation: Institute of Biochemistry, Christian-Albrechts University of Kiel, D-24118 Kiel, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Trad
authors.forename: Michel
authors.initials: M
authors.lastname: Riese
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shomali
authors.forename: Nina
authors.initials: N
authors.lastname: Hedeman
authors.forename: Timo
authors.initials: T
authors.lastname: Effenberger
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Inken
authors.initials: I
authors.lastname: Lorenzen
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000072198:ADAM17 Protein; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017434:Protein Structure, Tertiary / Q000235:genetics; D059016:Tumor Microenvironment
chemical_list: D019483:Disintegrins; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human