IGFBP7：免疫治療新靶點(diǎn)

IGFBP7：免疫治療新靶點(diǎn)前

言胰島素樣生長(zhǎng)因子結(jié)合蛋白7（IGFBP7）是胰島素超家族的生長(zhǎng)促進(jìn)肽成員，可與胰島素和IGF結(jié)合，調(diào)控細(xì)胞生長(zhǎng)和分化。IGFBP7在不同的腫瘤類(lèi)型中表現(xiàn)出抑制或促進(jìn)腫瘤生長(zhǎng)的“自相矛盾”活性。研究發(fā)現(xiàn)IGFBP7可增強(qiáng)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(biāo)志物。01IGFBP7的生理學(xué)和病理學(xué)意義IGFBP7在多種組織中表達(dá)，包括大腦、肝臟、胰腺和骨骼肌。IGFBP7通過(guò)調(diào)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(jié)合來(lái)發(fā)揮功能。通過(guò)與胰島素或IGF結(jié)合，激活下游三個(gè)重要的信號(hào)轉(zhuǎn)導(dǎo)通路：IRS-PI3K-AKT-mTOR、Ras-MEK-ERK和Ras-MAPK，誘導(dǎo)蛋白合成、細(xì)胞增殖、生長(zhǎng)維持及抗凋亡。IGFBP7在IGF依賴型或IGF獨(dú)立型癌癥類(lèi)型中表達(dá)有所差異。在IGF獨(dú)立型癌癥中，IGFBP7可促進(jìn)腫瘤細(xì)胞生長(zhǎng)、血管生成、上皮間質(zhì)轉(zhuǎn)化(EMT)和細(xì)胞凋亡。IGFBP7還在多種類(lèi)型的癌癥中呈現(xiàn)腫瘤抑制活性。通過(guò)與CD93結(jié)合，IGFBP7破壞腫瘤血管生成并增強(qiáng)免疫浸潤(rùn)，進(jìn)而增強(qiáng)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(biāo)志物，包括急性腎損傷、心衰和癌癥。IGFBP7和癌癥相關(guān)的潛在機(jī)制和途徑。（源自：/10.3389/fonc.2020.00727）02IGFBP7從實(shí)驗(yàn)室到臨床應(yīng)用IGFBP7在胃癌、前列腺癌、結(jié)直腸癌、膀胱癌和食道癌中表達(dá)上調(diào)。IGFBP7在腫瘤生成中的復(fù)雜生物學(xué)作用和分子機(jī)制仍然是臨床前關(guān)注的焦點(diǎn)。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(yīng)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(jī)制。Sun團(tuán)隊(duì)使用IGFBP7抗體（貨號(hào)：13100-R003，義翹神州）和CD93抗體（貨號(hào)：12589-MM01，義翹神州）阻斷IGFBP7和CD93相互作用。通過(guò)免疫熒光染色檢測(cè)組織樣本中IGFBP7的表達(dá)情況。Yamamoto團(tuán)隊(duì)利用重組IGFBP7蛋白（貨號(hào)：13100-H08H，義翹神州）研究LRP1的配體。用于流式細(xì)胞術(shù)檢測(cè)添加人源CD93單抗（貨號(hào)：12589-MM01，義翹神州）或IGFBP7單抗（貨號(hào)：13100-R003，義翹神州）可顯著降低IGFBP7蛋白與CD93-HEK293T細(xì)胞的結(jié)合，研究認(rèn)定IGFBP7是CD93的配體。（對(duì)照組為野生型HEK293T細(xì)胞（紅色），實(shí)驗(yàn)組為轉(zhuǎn)染CD93的HEK293T細(xì)胞。源自：doi:10.1126/scitranslmed.abc8922）用于免疫熒光檢測(cè)對(duì)來(lái)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(jìn)行染色，結(jié)果發(fā)現(xiàn)IGFBP7在腫瘤脈管系統(tǒng)中表達(dá)上調(diào)。IGFBP7（綠色）和CD31（紅色）。（源自：doi:10.1126/scitranslmed.abc8922）用于LC-MS/MS質(zhì)譜檢測(cè)評(píng)估了不同濃度下HMGB1（貨號(hào)：10326-H08H，義翹神州）、IGFBP7（貨號(hào)：13100-H08H，義翹神州）、SPARC（貨號(hào)：10929-H08H，義翹神州）、LIF（貨號(hào)：14890-H08H，義翹神州）等重組蛋白與LRP1之間的結(jié)合親和力，結(jié)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(chǎn)品IGFBP7Protein,Human,Recombinant(hFc&AVITag),Biotinylated,HPLC-verified,

Cat:13100-H41H-B

高純度：Purity≥90%asdeterminedbySDSandSEC-HPLC

結(jié)合活性ImmobilizedhumanCD93proteincanbindIGFBP7protein.TheEC50

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

Cat:13100-H07H1

結(jié)合活性ImmobilizedhumanIGFBP7ProteincanbindhumanCD93proteinwithalinearrangeof0.7-5.0μg/mL.更多IGFBP7明星產(chǎn)品貨號(hào)種屬標(biāo)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(xiàn)】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