Extracellular pressure stimulates adhesion of sarcoma cells via activation of focal adhesion kinase and Akt

• Published in: The American journal of surgery Vol. 200; no. 5; pp. 610 - 614
• Main Authors: Perry, Brandon C., B.A, Wang, Shouye, Ph.D, Basson, Marc D., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2010; Elsevier; Elsevier Limited
• Subjects: Adhesion; Adhesives; Akt; AKT protein; Biocompatibility; Biological and medical sciences; Biomedical materials; Biotechnology; Blotting, Western; Bone cancer; Cell Adhesion; Cell adhesion & migration; Cell cycle; Cell Line, Tumor; Cell signaling; Densitometry; Enzyme Activation - physiology; Extracellular Space - physiology; Fibrosarcoma; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - metabolism; General aspects; Growth factors; Humans; Inhibitors; Kinases; Medical prognosis; Medical sciences; Metastases; Metastasis; Osteosarcoma; Phosphorylation; Pressure; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rhabdomyosarcoma; Sarcoma; Sarcoma - enzymology; Sarcoma - pathology; Signal Transduction; Stimulation; Surgery; Akt; Focal adhesion kinase; Sarcoma; Pressure; Cell signaling; Enzyme; Transferases; Akt protein kinase; Activation; Malignant tumor; Adhesion; Extracellular; Medicine; Signal transduction; Treatment; Surgery; Cell; Protein-tyrosine kinase; Cancer
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2010.07.013

Abstract Background The effect of extracellular pressure on adhesion and adhesiogenic focal adhesion kinase (FAK) and Akt signaling in sarcomas was investigated. Methods Human sarcoma cells (HT-1080 fibrosarcoma, KHOS-240S osteosarcoma, and A-673 rhabdomyosarcoma) were subjected to increased pressure followed by adhesion assay. Two cell lines were pretreated with the FAK inhibitor 1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) or Akt IV inhibitor, followed by Western analysis for activated FAK and Akt. Parallel studies were conducted in cells from a resected human fibrous histiosarcoma. Results Pressure increased adhesion in all 3 sarcoma lines and primary histosarcoma cells by 7% to 18% (n = 6; P < .01 each). Pressure activated FAK and Akt (n = 5; P < .01). Inhibiting FAK or Akt inhibited FAK or Akt phosphorylation and the stimulation of adhesion by increased pressure (n = 5 each; P < .01 each). Conclusions Pressure increases sarcoma cell adhesiveness via Akt and FAK. Perioperative manipulation or forces in lymphatic or circulatory systems may potentiate local recurrence or distant metastasis.