Bone Marrow Hematopoietic Stem Cells Promote Mesenchymal-epithilial Transition Of Prostate Cancer Cells Through IGFBP3

Objective:Prostate cancer is a major health problem worldwide,similarly to other forms of cancer,and it is more difficult to treat once it spreads to other organs in the body.Unlike Western countries such as Europe and the United States,the relative lag of screening for susceptible prostate cancer of China is that most of the newly diagnosed prostate cancer patients(about 70%)are already locally advanced or metastatic prostate cancer.Almost all patients with prostate cancer metastasize in the late stage,and bone metastasis is one of the most common metastatic events in the late stage.So far,our understanding of the mechanism of bone metastasis of prostate cancer is very limited.Unfortunately,the treatment currently available for bone metastasis is mainly palliative treatment.Although it can improve the quality of life of patients,this is far from enough.We still lack prevention,treatment of prostate cancer and effective method of bone metastasis.Based on previous studies,we have demonstrated the important role of bone marrow mesenchymal stem cells(BMSC)in the invasion,proliferation and epithelial-mesenchymal transition of prostate cancer cells.This paper aims to confirm that bone marrow hematopoietic stem cells(BMHSC)can promote prostate cancer cells to perform mesenchymal-epithelial transformation(MET),then further explore specific mechanisms for finding treatment strategies for the prevention and treatment of bone metastases in prostate cancer.These strategies may have a role in preventing or reversing the process of tumor metastasis.Content:1.To confirm that bone marrow hematopoietic stem cells can promote adhesion of prostate cancer stem cells and inhibit the stem of prostate cancer stem cells;2.To confirme that bone marrow hematopoietic stem cells promote mesenchymal-epithelial transformation of prostate cancer cells;3.To investigate the role of bone marrow hematopoietic stem cells in promoting mesenchymal-epithelial transformation of prostate cancer cells;Method:1.Through cell clone formation experiments,we compared the adhesion ability ofprostate cancer CD133+ C4-2 cells treated by the RPMI-1640 medium containing10% FBS,the conditioned medium of bone marrow hematopoietic stem cells,and conditioned medium of bone marrow mesenchymal stem cell,then we detected the expression of cell stem Marker CD133 by qPCR.2.The prostate cancer CD133+ C4-2 cells were treated with the above three groups of media,then the expression of mesenchymal and epithelial Marker were compared in RNA and protein levels by PCR and Western blot.3.Comparison of cytokines in conditioned medium of bone marrow hematopoietic stem cells and bone marrow mesenchymal stem cells by cytokine chip,and verify the selected cytokines that may promote MET in prostate cancer cells by cell experiments.Result:1.Bone marrow hematopoietic stem cell conditioned medium can promote the attachment of CD133+ C4-2 cells and inhibit the expression of stem Marker CD133.2.Bone marrow hematopoietic stem cell conditioned medium can increase the transcription and protein of E-cadherin in prostate cancer CD133+ C42 cells,and reduce the transcription and protein of N-cadherin.3.The expression of IGFBP3 in bone marrow hematopoietic stem cell culture medium was significantly higher than that in bone marrow mesenchymal stem cell culture medium,and the bone marrow hematopoietic stem cell culture medium supplemented with IGFBP3 neutralizing antibody show the expression of E-cadherin was decreased,and the expression of N-cadherin was increasing compared with bone marrow hematopoietic stem cell culture medium.In conclusion:1.Bone marrow hematopoietic stem cells(BMHSC)can promote the attachment of CD133+ C42 cells and inhibit the expression of stem Marker CD133;2.Bone marrow hematopoietic stem cells(BMHSC)promote mesenchymal-epithelial transformation of prostate cancer C4-2 cells mainly through IGFBP3.