ABSTRACT
BACKGROUND: Choriocarcinoma is a kind of trophoblastic neoplasm with highly aggressive phenotypes. Forkhead box D3 (FoxD3) is an embryonic and trophoblastic stem cel transcription factor. It plays important roles in different physical and pathological situations such as embryogenesis, carcinogenesis and tumor progression. OBJECTIVE:To investigate the role of FoxD3 in choriocarcinoma malignancy and the possible mechanism. METHODS:The human choriocarcinoma JAR cel line was employed in this study. The mRNA and protein expressions of genes were measured by quantitative RT-PCR (qRT-PCR) and western blot, respectively. The FoxD3 specific short hair RNA was applied to down-regulate gene expression. The cel proliferation was evaluatedin vitro by cel counting assay andin vivo by tumor growth. The migration/invasion was determined by transwel assay. The profile of FoxD3 targeted genes was investigated with an Agilent microarray and verified by qRT-PCR. RESULTS AND CONCLUSION: The FoxD3 mRNA and protein expressions in JAR cells were significantly higher than those in primarily cultured normal trophoblastic cells. Knockdown of FoxD3 by short hair RNA in JAR cells could inhibit cell proliferation and migration/invasionin vitro, and suppress thetumor growth with decreased β-human chorionic gonadotropin secretionin vivo. A profile of seven focal adhesion molecules (ITGA5, ITGB6, THBS4, COL6A3, VTN, NRXN3 and NLGN1) was verified to be targeted by FoxD3. Furthermore, knockdown of FoxD3 by short hair RNA could decrease the activation of focal adhesion kinase. All these findings suggest the overexpression of FoxD3 can contribute to the aggressive phenotype of choriocarcinoma JAR cells by regulating the profile of focal adhesion molecules and focal adhesion kinase.
ABSTRACT
BACKGROUND:Now, the bone marrow mesenchymal stem cel homing is thought to be mediated by adhesion molecules and chemokines, and this process involves bone marrow endothelial cel s, hematopoietic stem cel s, bone marrow microenvironment and its secreted or expressed molecules, in which, adhesion molecules may play an important role. OBJECTIVE:To explore the migrating and chemotactic mechanism of bone marrow mesenchymal stem cel s via acupoint injection into myocardial cel s by determining the expression of vascular cel adhesion molecule-1 and very late antigen-4. METHODS:Bone marrow mesenchymal stem cel s were cultured using adherent method, and the passage 3 cel s were used as seed cel s at a density of 1×1010/L. Sixty Sprague-Dawley rats were randomly divided into sham group, model group, myocardial injection group, and acupoint injection group, 15 rats in each group. The left coronary arteries of rats were ligated for establishing a model of myocardial infarction. At 72 hours after myocardial infarction, 0.3 mL bone mesenchymal stem cel s were transplanted into the Xinyu, Zhiyang, Tanzhong acupoints, respectively, in the acupoint injection group;while in the myocardial injection group, secondary thoracotomy was done, and 1.2 mL bone marrow mesenchymal stem cel s were equably transplanted into six sites in the feeding area of the left anterior descending artery and the surrounding myocardium. At 4 weeks after myocardial infarction, a multi-channel polygraph was adopted for detection of hemodynamic parameters, and the levels of serum vascular cel adhesion molecule-1 and very late antigen-4 were measured by ELISA. RESULTS AND CONCLUSION:The heart function of rats in the myocardial injection and acupoint injection groups were improved, and compared with the model group, the levels of serum vascular cel adhesion molecule-1 and very late antigen-4 were significantly higher in the myocardial injection and acupoint injection groups. However, there was no significant difference between the myocardial injection and acupoint injection groups. These findings suggest that vascular cel adhesion molecule-1 and very late antigen-4 may be one of the chemotactic mechanisms of bone mesenchymal stem cel s transplanted in myocardial infarction model rats by acupoint injection.