Granulocyte colony-stimulating factor receptor signals for β1-integrin expression and adhesion in bladder cancer

Objectives. To examine the association of granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor (G-CSFR) expression with increased beta(1)-integrin expression and determine the ability of autocrine G-CSFR signaling to promote bladder cancer cell adhesion by way of beta(1)-integrin. beta(1)-integrin is expressed at higher levels in more invasive bladder carcinoma cells and participates in the process of tissue invasion. Cancer cell invasion and metastasis in some ways mimic normal neutrophil behavior. In neutrophils, G-CSF acts through its receptor to enhance adhesion and migration. A significant fraction of bladder carcinoma has been reported to express both G-CSF and G-CSFR. Methods. We examined bladder carcinoma tissue samples obtained from segmental or radical cystectomy specimens for expression of G-CSF, G-CSFR, and beta(1)-integrin using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical methods. We determined the G-CSFR-mediated beta(1)-integrin adhesion using a static adhesion assay and the bladder cancer cell line 5637. Results. Eleven of 14 bladder cancer samples expressed G-CSFR. All I I G-CSFR positive tumors also expressed G-CSF, and the G-CSF/G-CSFR positive tumors had elevated beta(1)-integrin protein levels. All but one G-CSFR negative tumor demonstrated low beta(1)-integrin protein levels. In four G-CSF/G-CSFR positive tumors for which distant urothelium was available for examination, G-CSF, G-CSFR, and beta(1)-integrin expression was also increased. In the 5637 cell line, we demonstrated G-CSFR-mediated upregulation of beta(1)-integrin-dependent adhesion to fibronectin and laminin. Conclusions. G-CSF/G-CSFR expression in some bladder cancers appears to be an early event during malignant transformation that increases beta(1)-integrin expression and adhesion and thereby may promote tissue invasion. (C) 2004 Elsevier Inc.