Abstract 4333: The role of cancer-associated fibroblast-induced chemokine ligand 11 in tumor microenvironment contributes to the progression of oral cancer

Abstract

Abstract Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related death in Taiwan and worldwide. The prognosis of OSCC is usually poor because of its propensity of extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Recent studies showed carcinoma-associated fibroblasts (CAFs), a major type of tumor-surrounding stromal cell, generate certain mediators through which CAFs interact with tumors and contribute to cancer progression in numerous cancers. The orchestration between CAFs and cancer cells is complex and its underlying mechanism needs to be explored. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behavior of cancer cells. Using microarray analysis, we detected abundant expression of chemokine (C-C motif) ligand 11(CCL11), also named Eotaxin, secreted by CAFs and further be identified as a critical mediator in CAF-induced invasiveness. We planned to validate that CCL11 played a major role in the crosstalk between fibroblasts and OSCC cells via the paracrine manner. CCL11was found upregulated in CAFs than in normal fibroblasts via Western blot analysis. Cells lines of OSCC, Fadu and TW204, treated with recombinant CCL11 increased capabilities of sphere formation in ten days. Administration of CCL11 promoted migration and invasion abilities through induction of the epithelial-to-mesenchymal transdifferentiation with corresponding morphological alterations of cancer cells. Counteracting CCL11 activity diminished the aggressive phenotype of cancer cells induced by CAFs. We further studied the relationship between the expression of CCL11 in both CAFs and OSCC cells and clinical outcome in the patients with OSCC. As a result, a high CCL11 expression level was associated with poor prognosis in terms of nodal metastasis and survival. These results indicate that CAFs promote cancer invasiveness via a paracrine effect on microenvironmental CCL11 signaling and suggest that CCL11 is a potential prognostic biomarker that may be considered in therapeutic strategies for the treatment of patients with OSCC. Citation Format: Shin Nieh. The role of cancer-associated fibroblast-induced chemokine ligand 11 in tumor microenvironment contributes to the progression of oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4333. doi:10.1158/1538-7445.AM2017-4333