Expression profiles of angiogenic growth factors in squamous cell carcinomas of the head and neck

Abstract

Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has become a major target in experimental cancer therapies. This therapeutical approach requires a profound knowledge of growth factor profiles that contribute to tumor growth and progression. The respective knowledge is presently rather incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we studied expression of several angiogenic cytokines including VEGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in HNSCC in vivo and in vitro. In tumor tissues expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 15 tissue-corresponding HNSCC cultures revealed that VEGF, PDGF-AB and less frequently GM-CSF were secreted in high amounts of up to 13 ng/ml/10 6 cells. Twenty percent of the HNSCC cultures expressed only 1 cytokine in biologically active amounts, 60% 2 or 3 and 20% expressed the maximum of 4 cytokines simultaneously. Interestingly, we observed a distinct cytokine pattern: HNSCC cells secreting only 1 or 2 cytokines presented always with either VEGF and/or PDGF-AB, while G-CSF and GM-CSF were secreted primarily together with VEGF and PDGF-AB. The number of cytokines expressed by HNSCC cells correlated with the microvessel density of the original tumor and with the clinical outcome: tumors producing at least 3 cytokines revealed a significantly poorer patient prognosis. Our data indicate a major role for VEGF and PDGF-AB in HNSCC and that the additional secretion of G-CSF or GM-CSF might contribute to a poorer prognosis in patients suffering from these tumors.

Role of tumor‐derived proinflammatory cytokines GM‐CSF, TNF‐α, and IL‐12 in the migration and differentiation of antigen‐presenting cells in cervical carcinoma

“…Although a previous study suggested that high TNF-a production was associated with an increased disease-free survival in nonsmallcell lung carcinoma, we did not find such an association. 37 A study by Ninck et al 38 also found a relation between the expression of growth factors (such as GM-CSF) and disease-free survival, but not by GM-CSF alone. Disease-free survival correlated with a poorer prognosis when head and neck squamous cell carcinoma simultaneously produced 3 or more growth factors.…”

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

“…HNSCC cell lines 45 were cultured routinely in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (PAA Laboratorie, Cö lbe, Germany) and 1% penicillin/streptomycin (Sigma, St Louis, MO, USA) in an atmosphere containing 5% CO 2 . 293T cell line was cultured in the same medium without antibiotics.…”

“…Incubation with primary and secondary antibodies and detection with Vectastain ELITE ABC Kit (Vector Laboratories, Burlingame, CA, USA) was carried out as described. 45 An amplification step was performed with the Tyramide Signal Amplification kit (NEL700; Perkin-Elmer, Rodgau, Germany) according to manufacturer's instructions.…”

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…While chronic inflammation may promote tumorigenesis [5,20], the tumor cells themselves also attract immune cells through the secretion of a wide range of chemokines such as IL-8 (CXCL8 in human/CXCL2 in mouse), CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES), CXCL6 (huGCP-2), and KC (CXCL1), and cytokines such as IL-1β, IL-6, TNFα, GM-CSF, and G-CSF, thereby inducing inflammation [21][22][23][24][25][26][27][28][29][30][31][32]. Cytokines from tumors may regulate tumor growth or modify the anti-tumor immune responses [33][34][35][36].…”