7P - Anti-interleukin-6 receptor antibody suppressed oral squamous cell carcinoma by inhibiting tumor-stroma interaction

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 1
Topics Head and Neck Cancers
Translational Research
Presenter Hiroyuki Goda
Citation Annals of Oncology (2015) 26 (suppl_9): 1-7. 10.1093/annonc/mdv517
Authors H. Goda1, M. Okamoto2, K. Nakashiro1, N. Tokuzen1, H. Hamakawa1
  • 1Department Of Oral And Maxillofacial Surgery, Ehime University Graduate School of Medicine, 791-0295 - Toon/JP
  • 2Department Of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo/JP

Abstract

Aim/Background

Recent studies show that interleukin-6 (IL-6) plays an important role in cancer development and cancer stromal fibroblasts are necessary for steps in progression, such as angiogenesis. However, little is known about the prognostic significance of IL-6 to the biology and the carcinogenic potential of stromal fibroblasts for oral squamous cell carcinoma (OSCC). This study aimed to investigate the correlation between IL-6 and cancer stromal fibroblasts related angiogenesis and the utility of IL-6 as a therapeutic target in OSCC.

Methods

We evaluated expression levels of IL-6 in 53 OSCC tissues by immunohistochemical staining and established three pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from OSCC surgical specimens and the normal counterparts. The expression levels of IL-6 and VEGF of NF and CAF were evaluated using quantitative RT-PCR and ELISA. We investigated the effect of an anti-human/anti-mouse IL-6 receptor antibody on the growth of OSCC cell line in vitro and vivo.

Results

Serial immunohistochemical staining of OSCC specimens showed that the IL-6 was mainly limited to cancer stromal region. NF cells were positive for vimentin and negative for cytokeratin AE1/AE3 and α-SMA. CAF cells were vimentin and α-SMA positive and cytokeratin AE1/AE3 negative. We confirmed that CAF produced significant amounts of IL-6 and VEGF than NF. Moreover, IL-6 enhanced VEGF production in NF and CAF, thereby inducing angiogenesis. We examined the in vitro cell proliferation of OSCC cells and CAF cells by WST-8 assay. Neither humanized anti-IL-6 receptor monoclonal antibody nor exogenous IL-6 influenced the proliferation rate of SAS cells and CAF cells under condition of single culture. However, in vivo study the IL-6 antibody reduced tumor volume by 70%.

Conclusions

These data suggest that inhibition of the relationship between IL-6 and stromal fibroblasts offers new approaches to OSCC therapy.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.