Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma

• Published in: Journal of oral pathology & medicine 2018-09, Vol.47 (8), p.748-754
• Main Authors: Hirschi, Kelsey M., Chapman, Steven, Hall, Parker, Ostergar, Adam, Winden, Duane R., Reynolds, Paul R., Arroyo, Juan A.
• Format: Article
• Language: English
• Subjects: AKT; AKT protein; AXL; Axl protein; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cytokines; Cytokines - metabolism; Dentistry; Disease Progression; Down-Regulation - drug effects; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Humans; Inflammation; Inflammation Mediators - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Intercellular Signaling Peptides and Proteins - pharmacology; Intercellular Signaling Peptides and Proteins - physiology; interleukins; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Multiplex; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Oral cancer; Oral squamous cell carcinoma; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-akt - metabolism; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Squamous cell carcinoma; Tumor Cells, Cultured
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12738

Background Gas6 protein is involved in the progression of cancers and has been demonstrated to have a role in inflammation. Oral squamous cell carcinoma is a common form of oral cancer, and it commonly expresses Gas6. Our objective was to determine the effects of Gas6 on oral squamous cell carcinoma invasion and identify signaling molecules and cytokines associated with Gas6‐mediated invasion. Methods Ca9‐22 cells were cultured in the presence or absence of Gas6. Real‐time cell invasion was evaluated, and cultured cells were lysed for Western blot analysis. Cell medium was collected and assayed for cytokine elaboration. Results Treatment of cells with Gas6 resulted in: (i) increased invasion, (ii) increased expression of Gas6 and AXL receptor, (iii) reduced invasion when AXL was inhibited, (iv) decreased ERK activation, (v) increased AKT activation, and (vi) decreased secretion of G‐CSF, IL‐2, IL‐6, and IL‐8. Conclusions Gas6 increases invasion of oral squamous cell carcinoma, and the invasion correlates with the increased AKT and the downregulation of pro‐inflammatory cytokines. These results may prove useful in providing avenues that explain the role of Gas6 in the development and progression of oral squamous cell carcinoma.