Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Promote Malignant Growth of Cells from Head and Neck Squamous Cell Carcinomas In vivo

Abstract

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are used to ameliorate cancer therapy-induced neutropenia and mucositis. Yet, first data in head and neck squamous cell carcinoma (HNSCC) indicate an impaired long-term prognosis on G-CSF treatment, and previous studies showed a contribution of both factors to the progression of human epithelial tumors. Therefore, we investigate the role of G-CSF and GM-CSF in progression of tumor cells from human HNSCC. Both factors stimulated proliferation and migration of tumor cell lines established from patient tumors expressing G-CSF and GM-CSF and/or their receptors. Blockade of G-CSF and GM-CSF inhibited tumor cell invasion in a three-dimensional organotypic culture model. The contribution of both factors to tumor malignancy was further confirmed in nude mouse transplants in vivo. Invasive and malignant growth yielding a similar tumor phenotype as the original patient tumor was exclusively observed in G-CSF-and GM-CSF-expressing tumors and was associated with enhanced and persistent angiogenesis and enhanced inflammatory cell recruitment. Although factor-negative tumors grew somewhat faster, they were characterized by lack of invasion, reduced and transient angiogenesis, and large necrotic areas. These data provide evidence for a progression-promoting effect of G-CSF and GM-CSF in human HNSCC and suggest further detailed evaluation of their use in the therapy of these tumors. (Cancer Res 2006; 66(16): 8026-36)

Gene expression profiling of archival tongue squamous cell carcinomas provides sub-classification based on DNA repair genes

“…Using the DASL methodology, many of the genes identified as differentially expressed in cancer samples were similar to those previously identified from frozen samples i.e. TGFB1, SPP1, STAT-1, CSF2/3, PLAUR, MMP and PTGS2 (COX-2) (35,(37)(38)(39). EGFR is commonly found to be up-regulated in SCCHN and also the first protein to be targeted for antibody treatment (40).…”

Comparative Anticancer Effects of Flavonoids and Diazepam in Cultured Cancer Cells

“…28,29) Modulation of angiogenesis via VEGF system by black tea polyphenols has been proposed as a mechanism of chemopreventon of rat mammary carcinogenesis. 29) Flavonoids, active ingredients isolated from several plants, have been also introduced to inhibit tumor angiogenesis through decreasing VEGF expression and the release of the angiogenic peptide VEGF from U-343 and U-118 human glioma cells.…”

Granulocyte colony stimulating factor alters the phenotype of neuroblastoma cells: implications for disease-free survival of high-risk patients

“…Our results indicate that neuroblastoma cell lines do express the mRNA for the GCSF-receptor (Figure 1) and respond to exogenous GCSF stimulation. The propensity for tumor cells to respond to growth factors is readily observed in several types of cancer [9][10][11][12][13]. This documented response to growth factors, coupled with the observation that neuronal progenitor cells utilize GCSF as a growth and development factor in normal development [15] suggest that these cells either never lose GCSF receptor expression, or reclaim expression as part of functional changes during mutagenesis or oncogenesis [16].…”

“…Specifically, GCSF has been associated with tumor progression, increased invasiveness and poorer prognosis in tumors such as head and neck squamous cell carcinoma [9], non-small cell lung cancer [10,11], bladder [12] and prostate cancer [13]. The reported association between GCSF, GCSF receptors and other tumors led us to question whether GCSF has an effect on neuroblastoma tumor growth.…”