The Experimental Study On The Migration Of Human Mesenchymal Stem Cells And Prostate Cancer

Objective To investigate the migration behavior of human mesenchymal stemcells in response to prostate cancer.Methods The human prostate cancer cell line PC-3 were injected into theflank or axillary of SCID mice subcutaneously to establish human prostate cancerxenograft models. hMSCs were harvested from donor's ribs of human cadaverrenal transplantation and separated by density gradient centrifuge. hMSCs betweenpassages 4 to 6 were labeled with DAPI. DAPI-labeled hMSCs were injected intothe bearing cancer SCID mice by tail vein(five doses(106 cells/dose) of labeledMSCs over a 15～20-day period) or 0.5cm away from peritumor (one dose of 106cells) subcutaneously. 17 days after injection by tail vein,7 days,10days and14days after injection by peritumor subcutaneously,the mice were killed and theirtumors,livers,lungs,spleens and kidneys were harvested.Frozen sections andparaffin sections were used to observe the distribution of exogenous DAPI-labeledhMSCs in vivo by fluorescence microscope.We measured the expression ofprostate specific antigen (PSA) and prostate-specific membrane antigen (PSMA) intumor tissue by immunohistochemistry.We developed a two-dimensional in vitromodel with 1% low-melt agarose dissolved in Dulbecco modified Eaglemedium/F12.The PC-3 cells and hMSCs were plated in the exposed area of themodel.Then to observe the adhesion between PC-3 cells and hMSCs.Results In SCID mice injected with PC-3 subcutaneously,the tumor take ratewas 83.3%.The tumors were identified by pathology. The tumors were negative forPSA and PSMA by immunohistochemistry.17 days after injection hMSCs by tailvein,7 days,10days and 14days after injection hMSCs by peritumorsubcutaneously, DAPI-labeled hMSCs with blue nuclei were distributedextensively in the tumors.But no blue nucleus was seen in the livers,lungs,spleensand kidneys.The tumor growth was accelerated after injection hMSCs. In vitromodel,the PC-3 cells adhered to hMSCs after a day coculture.A significant increasein the adhesion of PC-3 cells to hMSCs was found at 4～7 days cocultures. Conclusions Exogenous purified hMSCs can migrate to prostate cancermicroenviroment in vivo.The PC-3 cells can adhere to hMSCs in vitro.