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Granulocyte‐colony‐stimulating factor enhances invasive potential of human head‐and‐neck‐carcinoma cell lines
Author(s) -
Noda Ichiro,
Fujieda Shigeharu,
Ohtsubo Toshio,
Tsuzuki Hideaki,
Tanaka Nobuyuki,
Sunaga Hiroshi,
Saito Hitoshi
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990105)80:1<78::aid-ijc16>3.0.co;2-s
Subject(s) - cell culture , granulocyte colony stimulating factor , haematopoiesis , cancer research , cytokine , biology , progenitor cell , hematopoietic growth factor , microbiology and biotechnology , pathology , stem cell , medicine , immunology , chemotherapy , genetics
Granulocyte‐colony‐stimulating factor (G‐CSF), a hematopoietic cytokine, regulates the proliferation and differentiation of granulocytic progenitor cells and functionally activated mature neutrophils. G‐CSF also affects non‐hematopoietic tumor cells by the binding of G‐CSF to its specific receptor (G‐CSFR) on the cells. In this study, we investigated the effect of G‐CSF on the invasive potential of head‐and‐neck carcinoma cells, and explored the intracellular events initiated by the binding of G‐CSF in tumor cells. In vitro treatment of head‐and‐neck‐carcinoma cell lines, IMC‐2, IMC‐3, KB, Ca9‐22, SCCKN and SCCTF, with recombinant G‐CSF (rG‐CSF) significantly augmented their invasive potential in dose‐ and time‐dependent manners. Among these cancer cells, IMC‐2, IMC‐3, KB and Ca9‐22 cells produced little G‐CSF, while large amounts of G‐CSF were produced by SCCKN and SCCTF cell lines. Anti‐G‐CSF antibody (Ab) abrogated the rG‐CSF‐enhanced invasiveness to the control level of that in untreated cancer cell lines. Immunocytochemical staining and Western blotting using anti‐G‐CSFR monoclonal antibody (MAb) revealed the expression of G‐CSFR on head‐and‐neck‐cancer cell lines exhibiting the enhancement of invasive activity by rG‐CSF. IMC‐2 cells, having the highest invasive ability among the cell lines used, showed augmentation of G‐CSFR expression on stimulation with rG‐CSF. Furthermore, stimulation of IMC‐2 cells with rG‐CSF induced rapid activation of tyrosine‐phosphorylated JAK1, suggesting that the G‐CSF signal may be transduced into the cells through G‐CSFR. Moreover, the gelatinolytic activity of IMC‐2 cells was enhanced by stimulation of rG‐CSF, and the enhanced invasiveness was inhibited on addition of the tissue inhibitors of metalloproteinases (TIMPs). These results suggest that exogenous rG‐CSF may increase the risk of metastasis and/or local recurrence in patients with G‐CSFR‐positive head‐and‐neck squamous‐cell carcinoma, via an invasive mechanism. Int. J. Cancer 80:78–84, 1999. © 1999 Wiley‐Liss, Inc.