Possible prognostic role of IL-17R in osteosarcoma

Abstract

These results suggest that IL-17R in OS might represent a marker of tumor metastasis potential.

IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells

“…Our data were in line with the previous study which showed that IL-17RA expression correlated with VEGF secretion and IL-17A sensitivity and thus represented a marker of tumor metastasis potential. 22 IL-17A had recently been reported to stimulate Stat3 activation through a positive feedback loop in inflammatory cells, fibroblasts, as well as the growth of B16 melanoma and MB49 bladder carcinoma. 27 As Stat3 activation in tumor cells and tumor-associated inflammatory cells played a critical role in tumor progression by augmenting tumor survival and tumor angiogenesis, and suppressing antitumor immunity, [24][25][26] we therefore detected the Stat3 activity in OS cells in response to IL-17A/IL-17RA interaction.…”

“…[18][19][20][21] In OS, previous study showed that U-2 OS cells which expressed higher level of IL-17RA were more sensitive to IL-17A, and secreted higher amounts of vascular endothelial growth factor (VEGF), whereas MG63 expressed lower level of IL-17RA, was not sensitive to IL-17A and secreted lower amount of VEGF, suggesting that IL-17RA expression was correlated with VEGF secretion. 22 Given that VEGF is well established as one of the key regulators of the new blood vessel formation (angiogenesis) which is a fundamental event in the process of tumor growth and metastatic dissemination, and was an important negative prognostic factor in OS, 23 we IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells Figure 1D, we found that IL-17RA expression was higher in tumor tissues from OS patients with metastasis than that in tumor tissues from OS patients without metastasis (p < 0.05). These findings suggested that IL-17A/IL-17RA signaling might be involved in metastasis of OS.…”

The expression of interleukin (IL)-17 and IL-17 receptor and MMP-9 in human pituitary adenomas

“…In the rheumatoid arthritis, the deficiency of IL-17R results in impaired expression of MMP-9 [31]. Moreover, in the osteosarcoma cell lines U-2, the high expression of IL-17R was associated with the high secretion of VEGF (venous endothelial growth factor) and sensitive to IL-17, suggesting that IL-17R may be a marker of tumor metastasis [32].…”

Emerging Cytokine Networks in Osteosarcoma

“…In stromal cells and fibroblasts, IL-17 induces the production of a variety of angiogenic mediators, including VEGF [90] . In fact, IL-17RA expression correlated with VEGF production by osteosarcoma lineages [91] .…”

“…Results from clinical trials demonstrated that osteosarcoma patients had higher IL-17 serum levels in comparison to healthy volunteers. Patients who had metastasis presented the highest IL-17 serum levels [91] . Such body of evidence indicates the IL-17 prognostic role for osteosarcoma, pointing out this interleukin as a potential therapeutic target [91,92] .…”