TY - JOUR
T1 - Tracking biodistribution of myeloid-derived cells in murine models of breast cancer
AU - Li, Jun
AU - Mai, Junhua
AU - Hinkle, Louis
AU - Lin, Daniel
AU - Zhang, Jingxin
AU - Liu, Xiaoling
AU - Ramirez, Maricela R.
AU - Zu, Youli
AU - Lokesh, Ganesh L.
AU - Volk, David E.
AU - Shen, Haifa
N1 - Funding Information:
Figure 4. T1 aptamer preferentially binds human bone marrow cells. (a) Human bone marrow cells were incubated with increasing concentrations of Cy5-labeled T1 or SCR aptamers, and flow cytometry was performed to detect aptamer-binding cells. (a) Separation of scramble-and T1 aptamer-binding human bone marrow hematopoietic cells. Aptamer concentration: 1.56 nM. (b) T1 aptamer concentration-dependent binding of human bone marrow hematopoietic cells. 4. Discussion 4. Discussion The myeloid-derived cells are comprised of multiple sub-populations of mature and immature cells.TIhnet hmisyestlouiddy-,dwereivheadv eceslhlso warne tchoamt pthreisTed1 aopf tmamuletripcloen ssuisbt-epnotlpyublaintidosntsh oef CmDa1tu1bre+Layn6dG i+mLmy6aCtulowre cgerlalns.u Ilno cthytisic sstuudb-yp, owpeu lhaatvioensohfocwenll st,hbauttthneo tTt1haepCtaDm11ebr cLoyn6siGsteLnytl6yC bindms tohneo CcyDt1ic1bsuLby-p6GopLuyla6tCion, ginrabnoutlhoctyutmic osruba-npdopnuolnat-itounm oofrcetilslss,u beus.t nWote thhea CveD1a1lsbo+Ldye6tGec−tLeyd6CThi1ghbminodninogcyttoic tshueb-CpDop1u1bla+tFio4n/8, 0in+ bmoathcr otpuhmaogre sa, nadlt hnooung-htubminodr intigsslueevse. lsWvea ryhadveep eanlsdoi ndgetoencttehde Ttu1mboirndminogd etloa nthde saCmDp1l1eb+sFo4u/r8c0e+. mReagcarrodplhesasgeosf,thaelthtuomugohr mbionddeiln, go ulrevsteulsd yvahrays pdreopveinddedinsgt roonn gthsue ptpuomrtofro rmdoedveell oapnidn gsaTm1 apslea suonuiqrcuee. Rpreogbaerdtolemssoonfi tothret utmumorogr rmowodthela,nodumr esttausdtyasihsa.s provided strong support for developing T1 as a uniquWee phraovbee rteoc menotlnyitsohro twumn othra gtrTo1watpht aanmde rmceatnasstearsvies. as a unique probe for tumor-targeted delivery of canWceer hthaevrea preeucetinctlayg esnhtosw[1n1 ]t.hTarte aTtm1 eanpttaomf 4eTr 1ctaunmsoerr-vbee aarisn ga municiequwei thprTo1b-ec ofnojru gtuatmedorl-iptaorsgoemteadl ddeolxiovreurybiocifn c(aTn1c-eDr othx)edrarpameuattiicc aalglyenintsh [ib11it]e.d Ttruematomregnrto owft4hTw1i tthuomuotrc-abuesairnigngse mveicree twoxitihci tTy1. -Acosnthjuegreataerde laiplaorsgoemnaulmdboexroorfuCbDici1n1b(+TL1y-6DGo+xL) yd6rCalowmagtircaanlluyl oicnyhtiicbicteeldls itnumciorcrulgartoiownt,hthewTit1h-oDuotx cpaaurstiicnlges sceavnebree ttoakxeicnituyp. Abys tthheesreec aelrles aan ldartgraen nspuomrtbeedr tooft hCeDtu11mbo+Lr yti6sGsu+eLyd6uCrilonwg gcerlalninuflioltcryattiico nc.elAlsl tienr ncairticvuellayt,iTon1-,Dthoex Tp1a-rDticolxe spaarreticclaersr iceadno bvee rtatoketnh eutpu mbyorthtiessseu ecewllhs earnedth teryanasrpeoirntetedr ntaol itzheed tbuymtohre ttiussmueo rdausrsioncgi acteedll ignrfailnturaloticoynt.icAcletellrsnaatnidvemlya,cTro1-pDhoaxg epsa.rtRicelseusl tasrefrocmarrtihede couvrerre nttostthued ytupmroovridtiessfuuertwhehresrueptphoeyrt aforer idnetverenloaplimzeedn tboyftTh1e atputmamorear-scsooncjiuagteadte gdracannucloercythtiecr aceplelsu taincsd. macrophages. Results from the current studyA pnroinvtiedree sfutirntgheorb ssueprvpaotrito fnorf rdoemvetlhoepmsteundty oifsTt1haatptTa1maepr-tcaomnejurgcaatnedoncalyncbeirntdhearafrpaecutitoicns.o f the CD11Abn+ Linyt6eGre+sLtyin6gC lowobsgerrvaantuioloncyfrtoesmi nthme ossttutdisys uise st.hOatnTe1poapsstiabmilietry ciasnpooonrlyT 1bianpdt aam ferracpteionne toraf titohne CinDto11thbe+Ltyis6sGu+eLsy. 6ICt hlowasgbraenenulwoceyltledsoicnu mmoesnttetidsstuheast.sOeqnue epnotisaslibpihliytysiicsalpaonodr Tb1ioalopgtaicmalerb aprernieertsraetxioisnt iinntsoid tehteh etisbsoudeys.t hIta thcaasn bbeleonc kwterallndspoocurtmoefnntuetdri ethnatst,smeqetuaebnotliiatel sp,hdyiasgicnaol satincdp rboiobelosg, aicnadl bbiagrrainerds semxiasltl imnsoildeec utlheed broudgys [t1h8a]t. cTahne bTl1ocakp ttaramnesrpofarltl soifnntouttrhieisnctsa,t emgeotrayb.oAliltteesr, ndaitaivgenloys,tTic1pmroigbhets,p arnefde rbeingt iaanlldy sbminadlla msuoblseectuolef thderuCgDs 1[11b8+].L yT6hGe+ LTy16 Calowptamgrearn uflaollcsytienst.oA tlthhiosucgahtetghoerbyo. dAylitserfinlaletdivwelyit,h Tim1mmaitguhret pPrMefNer-eMnDtiaSlClys dbuinridnga tsuumbosertgorof wththe ,CthDe1re1bar+Leya6lsGo+aLyla6rCgelownugmrabneurloofcymteastu. rAelgthraonuuglhoctyhtee sbiondcyircisu lfailtlieodn wanidthi nimthmeiantfularme mPMatoNry-MtiDssSuCess. Idtuisrvinegrytduimffiocru ltg,riofwnotthi,m tphoesrsei balree, toalsseop aar altaertghee mnuatmurbeegr raonf umloactyutrees gfrroamnutlhoecyimtems aintu criercPuMlaNti-oMnDanSCdsinbatsheed ionnflaflmowmacytotorymteitsrsyu,eass.bItotihs vpeorpyu dlaitfifoicnuslot,ficfenllostciamrrpyoasnsiabllme,otsot sidepenatriactael stehteo mf caetlul srue rgfarcaenmulaorckyetress [1fr]o. mFu ttuhree ismtumdiaetsuarree PnMeeNde-dMtDoSfuCrst hbearsuenddoenrs tfalonwd thcyetmomecehtaryn,i sams boof tthhepTo1puaplattaiomnesr –omf cyeelllos icdacrreyll ainnt earlamcotisotni.dentical set of cell surface markers [1]. Future studies are needed to further understand the mechanism of the T1 aptamer–myeloid cell interaction. Author Contributions: Conceptualization, J.L, J.M. and H.S.; Methodology, J.L., J.M., Y.Z., G.L.L.; Acquisition of data, J.L., L.H., D.L., J.Z., X.L.; Analysis and interpretation of data, J.L., J.M., D.E.V., H.S.; Writing-Original Draft Author Contributions: Conceptualization, J.L, J.M. and H.S.; Methodology, J.L., J.M., Y.Z., G.L.; Acquisition of data, J.L., L.H., D.L., J.Z., X.L.; Analysis and interpretation of data, J.L., J.M., D.V., H.S.; Writing-Original Draft Preparation, J.L.; Writing-Review & Editing, L.H., Y.Z., D.V., H.S.; Supervision, H.S.; Project Administration, Funding: This study was partially supported by grants from the National Cancer Institute (1R01CA193880, 1R01CA222959M.R.; Funding Acquand U54CA210181),isition, H.S. Golfers Against Cancer, and METAvivor.
Funding Information:
This study was partially supported by grants from the National Cancer Institute (1R01CA193880, 1R01CA222959 and U54CA210181), Golfers Against Cancer, and METAvivor.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/4
Y1 - 2019/4
N2 - A growing tumor is constantly secreting inflammatory chemokines and cytokines that induce release of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and macrophages, from the bone marrow. These cells not only promote tumor growth, but also prepare distant organs for tumor metastasis. On the other hand, the myeloid-derived cells also have phagocytic potential, and can serve as vehicles for drug delivery. We have previously identified thioaptamers that bind a subset of MDSCs with high a_nity and specificity. In the current study, we applied one of the thioaptamers as a probe to track myeloid cell distribution in the bone, liver, spleen and tumor in multiple murine models of breast cancer including the 4T1 syngeneic model and MDA-MB-231 and SUM159 xenograft models. Information generated from this study will facilitate further understanding of tumor growth and metastasis, and predict biodistribution patterns of cell-mediated drug delivery.
AB - A growing tumor is constantly secreting inflammatory chemokines and cytokines that induce release of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and macrophages, from the bone marrow. These cells not only promote tumor growth, but also prepare distant organs for tumor metastasis. On the other hand, the myeloid-derived cells also have phagocytic potential, and can serve as vehicles for drug delivery. We have previously identified thioaptamers that bind a subset of MDSCs with high a_nity and specificity. In the current study, we applied one of the thioaptamers as a probe to track myeloid cell distribution in the bone, liver, spleen and tumor in multiple murine models of breast cancer including the 4T1 syngeneic model and MDA-MB-231 and SUM159 xenograft models. Information generated from this study will facilitate further understanding of tumor growth and metastasis, and predict biodistribution patterns of cell-mediated drug delivery.
KW - 1R01CA222959 and U54CA210181)
KW - And METAvivor
KW - Biodistribution
KW - Breast cancer
KW - Golfers Against Cancer
KW - Myeloid-derived suppressor cell
KW - Thioaptamer This study was partially supported by grants from the National Cancer Institute (1R01CA193880
UR - http://www.scopus.com/inward/record.url?scp=85068385063&partnerID=8YFLogxK
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U2 - 10.3390/genes10040297
DO - 10.3390/genes10040297
M3 - Article
AN - SCOPUS:85068385063
SN - 2073-4425
VL - 10
JO - Genes
JF - Genes
IS - 4
M1 - 297
ER -