High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells

Abstract

Bone morphogenetic protein 2 (BMP2) signaling had significant roles in diverse pathological processes, such as cancer. Nevertheless, the interaction between BMP2 and carcinoma development remained largely unknown. In particular, the roles that BMP2 play in the development of liver cancer remained controversial, and mechanisms were unclear. BMP2 with strong osteogenic potential had been manufactured into various bone materials. However, cancer risk concerns were raised in recent years. Thus, we focused on analyzing the effects of exogenous BMP2 on the growth of liver cancer and the detailed mechanisms. We found that both intravenous injection of rhBMP2 and in vivo implantation of rhBMP2 materials could lead to the expansion of myeloid-derived suppressor cells (MDSCs) in peripheral blood and subsequently enhanced the infiltration of MDSCs into tumor in vivo. Furthermore, BMP2 signaling-activated MDSCs could secrete IL6 to enhance cell proliferation of liver cancer cells in vitro and facilitate liver cancer growth in vivo. Our study indicated that increased concentration of BMP2 within the peripheral blood could enhance liver cancer growth via the activation of MDSCs. In this study, the roles that BMP2 played in liver cancer growth were further confirmed and the detailed mechanisms about how BMP2 enhanced liver cancer growth were also elucidated.

Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line

“…BMP2 is a growth factor and plays an important role in bone formation, but recent studies found that BMP2 might also play a role in carcinoma progression. Higher BMP2 expression was found in the liver of patients with human hepatocellular carcinoma than that of normal liver tissues, and exogenous BMP2 injected into mice enhanced liver cancer growth through the activation of myeloid-derived suppressor cells to secret more IL6, which could promote cell proliferation of liver cancer cells [ 70 ]. Uncontrolled cell proliferation in healthy cells is a hallmark of the transformation to cancer cells [ 71 ].…”

Association between the expression levels of ADAMTS16 and BMP2 and tumor budding in hepatocellular carcinoma

“…As for BMP2, in the present study, patients with BCLC stage B-C had significantly higher BMP2 expression levels than patients with BCLC stage 0-A, suggesting the involvement of BMP2 in the progression and metastasis of HCC. Previous studies have demonstrated that BMP2 may promote HCC cell proliferation and invasion, thereby promoting malignant progression of HCC ( 20 , 21 , 44 ). As such, the results of the present study are in accordance with previously reported results.…”

A risk score model based on TGF-β pathway-related genes predicts survival, tumor microenvironment and immunotherapy for liver hepatocellular carcinoma

“…Plasminogen activator inhibitor 1 (SERPINE1, also known as PAI-1), is considered as a prognostic biomarker for gastric cancer, gliomas, and colorectal cancer [ 40 – 42 ], hepatocellular carcinoma [ 43 ]. SERPINE1 was also in an 8-gene prognostic by Lin et al [ 44 ] High expression of bone morphogenetic protein 2 (BMP2) could promote liver cancer cell growth through activating myeloid-derived suppressor cells [ 45 ]. Other four prognostic genes were less reported in LIHC research.…”