Research Paper Volume 13, Issue 17 pp 21216—21231

Dual roles of WISP2 in the progression of hepatocellular carcinoma: implications of the fibroblast infiltration into the tumor microenvironment

The infiltration of fibroblast cells into HCC tissues is related to HMGB1 after overexpression of WISP2. (A) HMGB1 was significantly upregulated after overexpression of WISP2 at the protein level using immunoblotting in HCC. (B) Immunoblotting was performed to determine the downregulated expression of HMGB1 in Hep3B-WISP2-shHMGB1. (C, D) Hepatic stellate LX2 cells treated with CM from Hep3B-WISP2 or CM from Hep3B-WISP2-shHMGB1, exhibited inhibited proliferation ability. (E) LX2 cells treated with CM from Hep3B-WISP2 exhibited enhanced migration ability, while exhibited inhibited migration ability after treated with CM from Hep3B-WISP2-shHMGB1. (F) Subcutaneous tumours in nude mice were induced via inoculation with Hep3B-Vector, Hep3B-WISP2-Mock, and Hep3B-WISP2-ShHMGB1 HCC cells, and the weights of tumours from Hep3B-WISP2-ShHMGB1 cells were significantly decreased. (G) Tumours generated from the Hep3B-WISP2-ShHMGB1 cells exhibited significantly decreased α-SMA expression and fibro-collagen deposition.

Figure 5. The infiltration of fibroblast cells into HCC tissues is related to HMGB1 after overexpression of WISP2. (A) HMGB1 was significantly upregulated after overexpression of WISP2 at the protein level using immunoblotting in HCC. (B) Immunoblotting was performed to determine the downregulated expression of HMGB1 in Hep3B-WISP2-shHMGB1. (C, D) Hepatic stellate LX2 cells treated with CM from Hep3B-WISP2 or CM from Hep3B-WISP2-shHMGB1, exhibited inhibited proliferation ability. (E) LX2 cells treated with CM from Hep3B-WISP2 exhibited enhanced migration ability, while exhibited inhibited migration ability after treated with CM from Hep3B-WISP2-shHMGB1. (F) Subcutaneous tumours in nude mice were induced via inoculation with Hep3B-Vector, Hep3B-WISP2-Mock, and Hep3B-WISP2-ShHMGB1 HCC cells, and the weights of tumours from Hep3B-WISP2-ShHMGB1 cells were significantly decreased. (G) Tumours generated from the Hep3B-WISP2-ShHMGB1 cells exhibited significantly decreased α-SMA expression and fibro-collagen deposition.