血小板增强骨髓间充质干细胞促肿瘤转移作用 .pdfVIP

血小板增强骨髓间充质干细胞促肿瘤转移作用

李竹倩;王梅;许文荣;朱伟;王倩倩;徐长根;纪宏革;陆益龙;赵向东;仇荣;孙丽;陈斌

【摘要】ObjectiveToinvestigatetheeffectofhumanbonemarrow

mesenchymalstemcells(BM-MSCs)stimulatedbyplateletsinvitroonthe

metastasisofcancercells.MethodsTheBM-MSCswereisolatedand

culturedinvitroandplateletsfromtheperipheralbloodofhealthypersons

werepurified.TheMSCs(control),platelets+MSCs,andplateletstreated

withculturemedia(CM)ofSGC-7901tumorcells+MSCs(T-platelets+

MSCs)werecultured,respectively,andtheMSCsandsupernatants(MSCs-

CMandSGC-7901-CM)werecollected,respectively,after24hours.The

expressionsofmarkersofcancer-associatedfibroblasts(CAF),suchasα-

SMAandVimentin,weredeterminedbyWestern-blotting.Theimmigration

abilityofBM-MSCswereanalyzedbyTranswellassay.ThelevelsofP-

selectininplateletsstimulatedbyMSCs-CMorSGC-7901-CMwere

detectedwithflowcytometry.ThemetastasismodelofgastriccancerSGC-

7901cellswasestablishedinBALB/cnudemicebytheinjectionoftail

vein,andthetumormetastasisinvivowasobserved.ResultsTheexpression

levelsofP-selectininplateletsstimulatedbyMSCs-CM([21.37±1.00]％)

orSGC-7901-CM([31.4±1.71]％weresignificantlyhigherthanthatinthe

control([3.17±0.40]％,t=27.85and29.18,P＜0.01).Theexpressionlevels

ofα-SMAandVimentininplatelets+MSCsgroup(0.79±0.08and0.88±

0.01)andT-platelets+MSCsgroup(0.90±0.06and0.96±0.04)were

significantlyhigherthanthatinthecontrol(0.64±0.02and0.75±0.05,t

=2.96and6.45forα-SMA,t=4.73and5.73forVimentin,P＜0.01).The

amountsofimmigrationcellsinplatelets+MSCsgroup(340.3±27.7)and

T-platelets±MSCsgroup(424.3±17.6)weresignificantlyhigherthanthat

inthecontrol(220.7±19.4,t=6.14and13.48,P＜0.01).Theinvivo

experimentalresultsshowedthatthemetastaticfociinplatelets±MSCs

group(4±2)andT-platelets±MSCsgroup(21±