Abstract:
Objective To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages (TAMs) on the invasion and metastasis of hepatocellular carcinoma (HCC).
Methods After exogenous IL-8 stimulation of THP-1 cells for 72h, the percentages of M1 and M2 TAMs were examined. RT-PCR and Western blot assays were used to study epithelial-mesenchymal transition (EMT), and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro. Lastly, 100 cases of HCC tissue samples were used to validate the correlation among TAM numbers, IL-8, and EMT features of HCC cells via immunohistochemistry (IHC) staining methods.
Results Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells. TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro. Finally, significant positive correlations among the numbers of TAMs, IL-8 expression, and N-cadherin expression were identified in primary HCC tissue samples (r=0.22, r=0.20, P < 0.05).
Conclusions IL-8 locally attracted and activated TAMs, and promoted M2 polarization of TAMs, which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.