Sprouty3, but Not Sprouty1, Expression Is Beneficial for the Malignant Potential of Osteosarcoma Cells

• Published in: International journal of molecular sciences 2021-11, Vol.22 (21), p.11944
• Main Authors: Kamptner, Anna Zita Mehira, Mayer, Christoph-Erik, Sutterlüty, Hedwig
• Format: Article
• Language: English
• Subjects: Adenoviruses; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical materials; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bone tumors; Brain cancer; Cell adhesion & migration; Cell growth; Cell Movement; Cell Proliferation; Colon; Ectopic expression; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; MAPK pathway; Membrane Proteins - genetics; Membrane Proteins - metabolism; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Osteosarcoma cells; Phenotypes; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation; Protein-tyrosine kinase receptors; Proteins; Roles; Sarcoma; Signal transduction; Sprouty3; Spry1; Spry3; Tumor Cells, Cultured; tumor promoter; Tumors; Tyrosine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111944

Sprouty proteins are widely accepted modulators of receptor tyrosine kinase-associated pathways and fulfill diversified roles in cancerogenesis dependent on the originating cells. In this study we detected a high expression of Sprouty3 in osteosarcoma-derived cells and addressed the question of whether Sprouty3 and Sprouty1 influence the malignant phenotype of this bone tumor entity. By using adenoviruses, the Sprouty proteins were expressed in two different cell lines and their influence on cellular behavior was assessed. Growth curve analyses and Scratch assays revealed that Sprouty3 accelerates cell proliferation and migration. Additionally, more colonies were grown in Soft agar if the cells express Sprouty3. In parallel, Sprouty1 had no significant effect on the measured endpoints of the study in osteosarcoma-derived cells. The promotion of the tumorigenic capacities in the presence of Sprouty3 coincided with an increased activation of signaling as measured by evaluating the phosphorylation of extracellular signal-regulated kinases (ERKs). Ectopic expression of a mutated Sprouty3 protein, in which the tyrosine necessary for its activation was substituted, resulted in inhibited migration of the treated cells. Our findings identify Sprouty3 as a candidate for a tumor promoter in osteosarcoma.