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

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.