Granulocyte colony-stimulating factor (G-CSF)-mediated signaling regulatestype IV collagenase activity in head and neck cancer cells

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, re gulates the proliferation and differentiation of granulocytic progenitor ce lls and functionally activated mature neutrophils. G-CSF also affects nonhe matopoietic tumor cells through its binding to the specific receptor (C-CSF R) on the cells. The type IV collagenase [matrix metalloproteinase 2 (MMP-2 )] is known to play a main role in the process of invasion and metastasis, but its regulation, for example, in expression or in activation, is not cle arly understood. In this study, we investigated the role of G-CSF in the re gulation of tumor cell invasion and the synthesis of MMP-2. G-CSFs producin g the head and neck carcinoma cell line T3M-I cells with metastatic ability and no G-CSF receptor (G-CSFR) expression were transfected with G-CSFR exp ression vector. In vitro treatment of G-CSFR-transfectant T3M-I cells with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in a reconstituted basement membrane (Matrigel) system compared with that of parental cells. Moreover, MMP-2 activity of G-CSFR-transfectant T3M-I ce lls was enhanced by the stimulation with rG-CSF, as assessed by gelatin zym ography. These results identify C-CSF as a regulator of MMP-2 and cellular invasion. (C) 2001 Wiley-Liss, Inc.