【原】IGFBP7：免疫治療新靶點(diǎn)

北京義翹神州 2024-10-18

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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。

01 IGFBP7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：https:///10.3389/fonc.2020.00727）

02 IGFBP7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。

03 IGFBP7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HEK 293T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

IGFBP7 Protein, Human, Recombinant (hFc & AVI Tag), Biotinylated, HPLC-verified, Cat: 13100-H41H-B

高純度：

Purity ≥ 90 % as determined by SDS-PAGE and SEC-HPLC

結(jié)合活性

Immobilized human CD93 protein can bind IGFBP7 protein. The EC₅₀ is 7-21 ng/mL.

IGFBP7 Protein, Human, Recombinant (K95R, His Tag), HPLC-verified, Cat: 13100-H07H1

結(jié)合活性

Immobilized human IGFBP7 Protein can bind human CD93 protein with a linear range of 0.7-5.0 μg/mL.

更多IGFBP7明星產(chǎn)品
貨號(hào)	種屬	標(biāo)簽	純度
13100-H56H-B	Human	His & AVI	≥90%^☆
13100-H02H	Human	hFc	＞85%
13100-H07H	Human	His	＞92%
13100-H08H	Human	His	＞92%
51125-M02H	Mouse	hFc	＞95%

☆：SEC-HPLC

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