IGFBP7：免疫治療新靶點

IGFBP7：免疫治療新靶點前

言胰島素樣生長因子結合蛋白7（IGFBP7）是胰島素超家族的生長促進肽成員，可與胰島素和IGF結合，調控細胞生長和分化。IGFBP7在不同的腫瘤類型中表現(xiàn)出抑制或促進腫瘤生長的“自相矛盾”活性。研究發(fā)現(xiàn)IGFBP7可增強治療性單克隆抗體的抗腫瘤作用，并在某些癌癥血清中含量高，正在成為多種疾病診斷的生物標志物。01IGFBP7的生理學和病理學意義IGFBP7在多種組織中表達，包括大腦、肝臟、胰腺和骨骼肌。IGFBP7通過調節(jié)組織中IGF的生物利用度和其受體（INSR-A、INSR-B、IGF-1R、IGF-2R）的結合來發(fā)揮功能。通過與胰島素或IGF結合，激活下游三個重要的信號轉導通路：IRS-PI3K-AKT-mTOR、Ras-MEK-ERK和Ras-MAPK，誘導蛋白合成、細胞增殖、生長維持及抗凋亡。IGFBP7在IGF依賴型或IGF獨立型癌癥類型中表達有所差異。在IGF獨立型癌癥中，IGFBP7可促進腫瘤細胞生長、血管生成、上皮間質轉化(EMT)和細胞凋亡。IGFBP7還在多種類型的癌癥中呈現(xiàn)腫瘤抑制活性。通過與CD93結合，IGFBP7破壞腫瘤血管生成并增強免疫浸潤，進而增強CD93單克隆抗體的免疫治療效果。隨著研究的深入，IGFBP7正在成為各種疾病的生物標志物，包括急性腎損傷、心衰和癌癥。IGFBP7和癌癥相關的潛在機制和途徑。（源自：/10.3389/fonc.2020.00727）02IGFBP7從實驗室到臨床應用IGFBP7在胃癌、前列腺癌、結直腸癌、膀胱癌和食道癌中表達上調。IGFBP7在腫瘤生成中的復雜生物學作用和分子機制仍然是臨床前關注的焦點。截至2023年8月，臨床研究主要集中在IGFBP7在急性腎損傷和心衰中的作用。03IGFBP7在研究中的應用IGFBP7蛋白和抗體用于研究腫瘤微環(huán)境和配受體相互作用機制。Sun團隊使用IGFBP7抗體（貨號：13100-R003，義翹神州）和CD93抗體（貨號：12589-MM01，義翹神州）阻斷IGFBP7和CD93相互作用。通過免疫熒光染色檢測組織樣本中IGFBP7的表達情況。Yamamoto團隊利用重組IGFBP7蛋白（貨號：13100-H08H，義翹神州）研究LRP1的配體。用于流式細胞術檢測添加人源CD93單抗（貨號：12589-MM01，義翹神州）或IGFBP7單抗（貨號：13100-R003，義翹神州）可顯著降低IGFBP7蛋白與CD93-HEK293T細胞的結合，研究認定IGFBP7是CD93的配體。（對照組為野生型HEK293T細胞（紅色），實驗組為轉染CD93的HEK293T細胞。源自：doi:10.1126/scitranslmed.abc8922）用于免疫熒光檢測對來自正常組織的胰腺、皮膚和原位KPC、皮下植入B16的腫瘤樣本進行染色，結果發(fā)現(xiàn)IGFBP7在腫瘤脈管系統(tǒng)中表達上調。IGFBP7（綠色）和CD31（紅色）。（源自：doi:10.1126/scitranslmed.abc8922）用于LC-MS/MS質譜檢測評估了不同濃度下HMGB1（貨號：10326-H08H，義翹神州）、IGFBP7（貨號：13100-H08H，義翹神州）、SPARC（貨號：10929-H08H，義翹神州）、LIF（貨號：14890-H08H，義翹神州）等重組蛋白與LRP1之間的結合親和力，結果發(fā)現(xiàn)HMGB1（6.4nM）、IGFBP7（11nM）、SPARC（41nM）等親和力較高，LIF（＞200nM）親和力較低。（源自：doi:

10.1016/j.matbio.2022.08.007）?義翹神州IGFBP7明星產品IGFBP7Protein,Human,Recombinant(hFc&AVITag),Biotinylated,HPLC-verified,

Cat:13100-H41H-B

高純度：Purity≥90%asdeterminedbySDSandSEC-HPLC

結合活性ImmobilizedhumanCD93proteincanbindIGFBP7protein.TheEC50

is7-21ng/mL.IGFBP7Protein,Human,Recombinant(K95R,HisTag),HPLC-verified,

Cat:13100-H07H1

結合活性ImmobilizedhumanIGFBP7ProteincanbindhumanCD93proteinwithalinearrangeof0.7-5.0μg/mL.更多IGFBP7明星產品貨號種屬標簽純度\o"/recombinant-proteins/human-igfbp7-13100-h56h-b"13100-H56H-BHumanHis&AVI≥90%☆\o"/recombinant-proteins/human-igfbp7-13100-h02h"13100-H02HHumanhFc＞85%\o"/recombinant-proteins/human-igfbp7-13100-h07h"13100-H07HHumanHis＞92%\o"/recombinant-proteins/human-igfbp7-13100-h08h"13100-H08HHumanHis＞92%\o"/recombinant-proteins/mouse-igfbp7-51125-m02h"51125-M02HMousehFc＞95%☆：SEC-HPLC【參考文獻】1.QiaoyunZhao,etal.IncreasedIGFBP7ExpressionCorrelateswithPoorPrognosisandImmuneInfiltrationinGastricCancer.JournalofCancer2021.doi:10.7150/jca.50370.2.YiX,etal.IGFBP7andtheTumorImmuneLandscape:ANovelTargetforImmunotherapyinBladderCancer.Front.Immunol.2022.doi:10.3389/fimmu.2022.898493.3.CD93BlockadeStabilizesTumorVasculaturetoImproveTherapyResponse.CancerDiscovery(2021)11(10):2368.doi:10.1158/2159-8290.Cd-rw2021-113.4.

HuangX,etal.TheDiagnosticValueofSerumIGFBP7inPatientswithEsophagealSquamousCellCarcinoma.JCancer2019,10(12):2687-2693.5.JinL,etal.InsulinGrowthFactorBindingProtein7(IGFBP7)-RelatedCancerandIGFBP3andIGFBP7Crosstalk.FrontiersinOncology,2020./10.3389/fonc.2020.00727.6.YamanakaY,etal.Inhibitionofinsulinreceptoractivationbyinsulin-likegrowthfactorbindingproteins.JBiolChem.1997.doi:10.1074/jbc.272.49.30729.7.OhY.,etal.Synthesisandcharacterizationofinsulin-likegrowthfactor-bindingprotein(IGFBP)-7.Recombinanthumanmac25proteinspecificallybindsIGF-I-II.JBiolChem.1996.doi:10.1074/jbc.271.48.30322.8.deMeytsP,etal.InsulinandIGF-Ireceptorstructureandbindingmechanism.In:SaltielAR,PessinJE,editors.MadameCurieBioscienceDatabase[Internet].Austin,TX:LandesBioscience(2000–2013).Availableonlineat:/books/NBK6192/9.LiY,etal.DownregulatedIGFBP7facilitateslivermetastasisbymodulatingepithelialmesenchymaltransitionincoloncancer.OncolRep2019,42(5):1935-1945.10.CaiX,etal.SilenceofIGFBP7suppressesapoptosisandepithelialmesenchymaltransformationofhighglucoseinduced-podocytes.ExpTherMed2018,16(2):1095-1102.11.SunY,etal.BlockadeoftheCD93PathwayNormalizesTumorVasculaturetoFacilitateDrugDeliveryandImmunotherapy.SciTransMed,2021.doi:10.1126/scitranslmed.abc8922.12.Gao,J.,etal.IGFBPrP1affectstheproliferation,apoptosisandmacrophagepolarizationofendometrialcancercellsbyregulatingthePI3K/AKTpathway.ExperimentalandTherapeuticMedicine,2023./10.3892/etm.2023.11868.13.Y.Xie,etal.,Tissueinhibitormetalloproteinase-2(TIMP-2)?IGF-bindingprotein-7(IGFBP7)levelsareassociatedwithadverseoutcomesinpatientsintheintensivecareunitwithacutekidneyinjury,ssssKidneyInternational,2019,doi:10.1016/j.kint.2019.01.020.14.Zhang,L.,etal.Insulin-likegrowthfactor-bindingprotein-7(IGFBP7)linkssenescencetoheartfailure.NatureCardiovascularResearch,2022./10.1038/s44161-022-00181-y.15.Bolomsky,etal.Insulinlikegrowthfactorbindingprotein7(IGFBP7)expressionislinkedtopoorprognosisbutmayprotectfrombonediseaseinmultiplemyeloma.BMC,2015./10.1186/s13045-014-0105-1.16.SmithE,etal.IGFBP7isassociatedwithpoorprognosisinoesophagealadenocarcinomaandisregulatedbypromoterDNAmethylation.BrJCancer,2014./10.1038/bjc.2013.783.17.Qiu,B.,etal.DiagnosticValueofSerumInsulin-LikeGrowth