Showing papers by "Sven Saussez published in 2013"
TL;DR: Clinical observations and experimental data suggest that MIF plays a pivotal role in the progression of head and neck squamous cell carcinoma and a significant difference between disease-free survival curves for local and nodal recurrence, and overall survival curve is disclosed.
Abstract: The present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC). Tumor tissue expression (MIF immunostaining) and plasma levels (ELISA) of MIF were determined in HNSCC patients and correlated with tumor recurrence and metastasis, and overall survival. Furthermore, the impact of MIF expression on cell proliferation and anticancer drug sensitivity was examined in murine squamous carcinoma cell line SCCVII after MIF knockdown (MIF-KD). As revealed by quantitative analysis of MIF immunostaining, tumor progression was accompanied by an increase in mean optical density (MOD) and labeling index (LI). Likewise, an elevation of MIF serum levels was noted in HNSCC patients (n = 66) versus healthy individuals (n = 16). Interestingly, comparison of laryngeal carcinoma patients on the basis of MIF tissue expression (high expression, LI ≥ 47, versus low expression, LI < 47) disclosed a significant difference between disease-free survival curves for local and nodal recurrence, and overall survival curve. In vitro, MIF knockdown in murine SCCVII cells resulted in reduced cell proliferation and a decrease in cell motility. In mice inoculated with SCCVII cells, MIF-KD tumors grew more slowly and also appeared more sensitive to chemotherapy. Both clinical observations and experimental data suggest that MIF plays a pivotal role in the progression of HNSCC.
33 citations
TL;DR: The inhibitory effects of 4-IPP on cell proliferation and invasiveness strongly suggest that MIF is involved in proliferative activity and invasive properties of squamous carcinoma cells.
Abstract: Recent clinical observations and experimental studies of our group indicate that macrophage migration inhibitory factor (MIF) may contribute to tumor progression in head and neck squamous cell carcinomas (HNSCC). The present study was undertaken to examine the effects of the irreversible MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) on proliferation and invasiveness of the squamous carcinoma cell line SCCVII. Cell counting, crystal violet assay and flow cytometry were used to analyze the effects of 4-IPP on SCCVII cell growth. The impact of 4-IPP on cell invasiveness was assessed by Boyden chamber assay. Knockdown of the MIF receptor CD74 was achieved by transduction with lentiviral vectors encoding anti-CD74 shRNAs. As shown by immunofluorescence staining, SCCVII cells express both MIF and CD74. Decreased MIF immunoreactivity as a result of exposure to 4-IPP suggested a covalent modification of the cytokine. 4-IPP inhibited SCCVII cell proliferation and invasiveness. Moreover, the cytostatic effect of 4-IPP was enhanced by CD74 knockdown. The inhibitory effects of 4-IPP on cell proliferation and invasiveness strongly suggest that MIF is involved in proliferative activity and invasive properties of squamous carcinoma cells. In conclusion, MIF inhibition may open possibilities for target-directed treatment of head and neck squamous cell carcinoma.
32 citations
TL;DR: It is shown for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR, highlighting the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.
Abstract: We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.
14 citations
Journal Article•
TL;DR: The state of knowledge of MIF involvement in upper aero-digestive tract cancers is assessed and the therapeutic perspectives are analyzed to suggest that MIF could be an interesting biomarker in the diagnosis and monitoring of upper aerodigestives tract cancers.
Abstract: Macrophage migration inhibitory factor is a critical proinflammatory cytokine produced by cells of innate and adaptive immune system. MIF plays a key role in cell cycle regulation and in the pathogenesis of many cancers. Recently, MIF has been studied in the upper aerodigestive tract cancer for its involvement in tumor progression, invasion, proliferation and cell motility. In addition, MIF appears to be a mediator in angiogenesis and in the development of metastasis and locoregional lymph node, which are often associated with a poor prognosis. The mechanisms of action responsible for MIF involvement in tumor progression are not completely elucidated. However, the main effects of MIF are mediated by the CD74 receptor. MIF binding to its receptor is responsible for the activation of several signaling pathways (ERK1/2 - MAPK, JAB1 - CSN5, PI3K - Akt), the inhibition of p53 and the stimulation of angiogenic factors including VEGF and IL-8. The overexpression of MIF also causes a reduction of the anti-tumor activity of the immune system. Finally, MIF could be an interesting biomarker in the diagnosis and monitoring of upper aerodigestive tract cancers. In this paper, we assess the state of knowledge of MIF involvement in upper aero-digestive tract cancers and we analyze the therapeutic perspectives.
3 citations
TL;DR: The molecular alterations which have been identified in squamous intra-epithelial neoplasia are reviewed to clarify the clinical manifestations and to discuss the proposed histological classification.
Abstract: Aero-digestive tract squamous intra-epithelial neoplasia is a disease whose genetic and epigenetic features lead to clinical signs and well codified histologic features. This publication aims to review the molecular alterations which have been identified in these lesions, to clarify the clinical manifestations and to discuss the proposed histological classification.
2 citations