Heparanase-induced proliferation and inhibition of apoptosis are associated with the phosphatase and tensin homologue deleted on chromosome 10/focal adhesion kinase signaling pathway in multiple myeloma

Abstract

Heparanase (HPSE) has an important effect on the proliferation, invasion, metastasis, and drug resistance of tumor cells. HPSE can promote proliferation and inhibit apoptosis of various solid tumor cells. Previous studies regarding the function of HPSE in multiple myeloma (MM) have primarily focused on tumor invasion and metastasis, whereas few studies have examined the proliferation and apoptosis of MM and the mechanisms associated with HPSE. This study recruited patients with MM and isolated MM cells (RPMI8226, LP-1) were isolated to measure the expression levels of HPSE, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and focal adhesion kinase (FAK) proteins to elucidate their roles in tumor formation. Compared with non-tumor patients, the mRNA and protein expression levels of HPSE and FAK in MM patients increased, whereas the levels of PTEN mRNA and protein decreased. Thus, the increase of HPSE coincided with an increase of FAK and a decrease of PTEN. MM cells exhibiting high HPSE expression exhibited increased proliferation and decreased AS2O3-induced apoptosis. These results indicate that changes in HPSE expression affect the proliferation and apoptosis of MM cells and this mechanism may be associated with the PTEN/FAK signaling pathway. Gene transfection needs proper vector, and proper gene transport system can improve transfection efficiency. In this paper, magnetic nanoparticles were transfected with overexpressed HPSE, and to detect the transfection efficiency and the proliferation ability of MM cells in the control group. The results showed that the cells transfected with magnetic nanoparticles had higher transfection efficiency and higher gene expression level. The results of this experiment provide a new way to explore new cancer therapy genes.