Interleukin‑8 promotes prostate cancer bone metastasis through upregulation of bone sialoprotein

Abstract

The aim of the present study was to investigate whether interleukin-8 (IL-8) enhances the ability of prostate cancer bone metastasis by influencing the coding level of bone sialoprotein (BSP). Cultured prostate cancer cell lines LNCaP (androgen dependent) and DU145 (androgen independent) were divided into three groups: IL-8 treatment group; IL-8 receptor inhibitor (SB225002) treatment group; and control group. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect BSP protein and mRNA expression levels. Matrigel and bone adhesion experiments were used to detect the invasiveness of cancer cells and bone adhesion changes. Compared with the control group, western blotting and RT-qPCR results indicated that BSP protein and mRNA levels in LNCaP and DU145 were significantly upregulated following IL-8 treatment. Matrigel experiments indicated that following IL-8 treatment, the invasiveness of LNCaP and DU145 cells was significantly increased. The results of bone adhesion experiments indicated that following IL-8 treatment, the number of DU145 cells adhered to the surface of the bone was increased, compared with the control group. Following treatment of both cell lines with SB225002, western blotting and RT-qPCR results indicated that the expression levels of BSP protein and mRNA were significantly downregulated. Matrigel experiments indicated that following SB225002 treatment, the invasiveness of LNCaP and DU145 cells was significantly reduced. The number of DU145 cells adhered to the surface of the bone was reduced, compared with the untreated group. Therefore, IL-8 may promote prostate cancer bone metastasis by enhancing BSP regulation.

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer

“…Another group looking at factors overexpressed by an osteogenic PCa xenograft identified CXCL8, which suggests a role for CXCL8 in osteogenesis in addition to its previously found role in promoting osteolysis ( 51 ). In another study, CXCL8 upregulated PCa cell expression of bone sialoprotein (BSP), an extracellular bone matrix protein, and increased PCa invasion and adhesion to bone chips in vitro , showing PCa cells can contribute to bone remodeling by producing bone matrix proteins and that CXCL8 has a role in this process as well as in the process of PCa metastasis to bone ( 52 ). The role of CXCL8 in bone remodeling and tumor progression makes it ideal for therapeutic targeting.…”

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

“…BSP and OPN have been more extensively studied than other SIBLING proteins. [24][25][26][27][28][29] These two proteins have been identified as primary inducers in the progression of PCa metastasis, especially bone metastasis. As mentioned previously, BSP and OPN contain an integrin-binding RGD sequence, which can bind to αVβ3 on the cell surface.…”

IL-8 Produced Via Bidirectional Communication Between Prostate Cancer and M2 Macrophages as a Potential Diagnostic and Prognostic Biomarker

“…The IL-8-regulated chemokine receptor CXCR7 stimulates epidermal growth factor receptor (EGFR) signaling to promote the growth 8 and invasion of PCa, 9 which promote PCa bone metastasis by enhancing bone sialoprotein (BSP) regulation. 10 However, the interactions between M2 macrophages and PCa cells that promote the expression of IL-8 and the subsequent progression of PCa remain unexplored. Additionally, the molecular mechanisms associated with IL-8 in PCa regarding their effects on diagnosis and prognosis have not been comprehensively explored.…”