IL-6 Promotes Cell Growth and Is Associated With Poor Prognosis In Patients With Oral Cancer

Abstract

Abstract Interleukin-6 (IL-6) is a pleiotropic inflammatory cytokine that regulates growth and differentiation of various types of malignant tumors, including oral cancers. Compared to healthy controls, the levels of IL-6 are elevated in sera of patients with oral cancer. In this study, the role of IL-6 in the growth regulation of oral cancer cells was evaluated. The effects of IL-6 on cell growth were evaluated by expressing IL-6 cDNA into the human tongue cancer cell line (SAS), resulting in high-producer clones. In vivo, the effects of tumor-derived IL-6 on growth were studied by using an experimental vaccine model. Two stable clones, consisting of low-producer (IL-6LE), and high-producer (IL-6OE), were subcutaneously inoculated on the flank of each severe combined immune-deficient (SCID) mice. A total of 111 surgically treated HNSCC patients were studied. IL-6 and STAT3 levels were measured by immunohistochemical staining and correlated with clinicopathological variables and patient survival. Treatment of recombinant IL-6 and overexpression of IL-6 by intorducing IL-6 into SAS cells significantly increased clonogenic ability and cell proliferation in vitro compared to the parental SAS cells and the vector controls. In animal model, a statistically significant difference of tumor weight was obtained between the IL-6LE and IL-6OE (*P=0.024) groups in experiment. Clinical data revealed significant relationships between IL-6 and stage*, lymph node metastasis*, recurrence**, disease-free survival* and overall survival* (P < 0.01; *P < 0.05). These findings strongly support the hypothesis that IL-6 acts as a significant autocrine growth factor in vivo and in vivo oral cancers.