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IGFBP7:免疫治疗新靶点

前  言

胰岛素样生长因子结合蛋白7(IGFBP7)是胰岛素超家族的生长促进肽成员,可与胰岛素和IGF结合,调控细胞生长和分化。IGFBP7在不同的肿瘤类型中表现出抑制或促进肿瘤生长的“自相矛盾”活性。研究发现IGFBP7可增强治疗性单克隆抗体的抗肿瘤作用,并在某些癌症血清中含量高,正在成为多种疾病诊断的生物标志物。

01 IGFBP7的生理学和病理学意义

IGFBP7在多种组织中表达,包括大脑、肝脏、胰腺和骨骼肌。IGFBP7通过调节组织中IGF的生物利用度和其受体(INSR-A、INSR-B、IGF-1R、IGF-2R)的结合来发挥功能。通过与胰岛素或IGF结合,激活下游三个重要的信号转导通路:IRS-PI3K-AKT-mTOR、Ras-MEK-ERK和Ras-MAPK,诱导蛋白合成、细胞增殖、生长维持及抗凋亡。

IGFBP7在IGF依赖型或IGF独立型癌症类型中表达有所差异。在IGF独立型癌症中,IGFBP7可促进肿瘤细胞生长、血管生成、上皮间质转化(EMT)和细胞凋亡。IGFBP7还在多种类型的癌症中呈现肿瘤抑制活性。通过与CD93结合,IGFBP7破坏肿瘤血管生成并增强免疫浸润,进而增强CD93单克隆抗体的免疫治疗效果。随着研究的深入,IGFBP7正在成为各种疾病的生物标志物,包括急性肾损伤、心衰和癌症。

IGFBP7和癌症相关的潜在机制和途径。

(源自:https://doi.org/10.3389/fonc.2020.00727)

02 IGFBP7从实验室到临床应用

IGFBP7在胃癌、前列腺癌、结直肠癌、膀胱癌和食道癌中表达上调。IGFBP7在肿瘤生成中的复杂生物学作用和分子机制仍然是临床前关注的焦点。截至2023年8月,临床研究主要集中在IGFBP7在急性肾损伤和心衰中的作用。

03 IGFBP7在研究中的应用

IGFBP7蛋白和抗体用于研究肿瘤微环境和配受体相互作用机制。Sun团队使用IGFBP7抗体(货号:13100-R003,义翘神州)CD93抗体(货号:12589-MM01,义翘神州)阻断IGFBP7和CD93相互作用。通过免疫荧光染色检测组织样本中IGFBP7的表达情况。Yamamoto团队利用重组IGFBP7蛋白(货号:13100-H08H,义翘神州)研究LRP1的配体。

用于流式细胞术检测  

添加人源CD93单抗(货号:12589-MM01,义翘神州)IGFBP7单抗(货号:13100-R003,义翘神州)可显著降低IGFBP7蛋白与CD93-HEK293T细胞的结合,研究认定IGFBP7是CD93的配体。(对照组为野生型HEK 293T细胞(红色),实验组为转染CD93的HEK293T细胞。源自:doi: 10.1126/scitranslmed.abc8922)

用于免疫荧光检测  

对来自正常组织的胰腺、皮肤和原位KPC、皮下植入B16的肿瘤样本进行染色,结果发现IGFBP7在肿瘤脉管系统中表达上调。IGFBP7(绿色)和CD31(红色)。(源自:doi: 10.1126/scitranslmed.abc8922)

用于LC-MS/MS质谱检测  

评估了不同浓度下HMGB1(货号:10326-H08H,义翘神州)、IGFBP7(货号:13100-H08H,义翘神州)、SPARC(货号:10929-H08H,义翘神州)、LIF(货号:14890-H08H,义翘神州)等重组蛋白与LRP1之间的结合亲和力,结果发现HMGB1(6.4nM)、IGFBP7(11nM)、SPARC(41nM)等亲和力较高,LIF(>200nM)亲和力较低。(源自:doi: 10.1016/j.matbio.2022.08.007)

✦义翘神州IGFBP7明星产品

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

高纯度:

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

结合活性

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

结合活性

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

更多IGFBP7明星产品

货号

种属

标签

纯度

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

【参考文献】

 1. Qiaoyun Zhao, et al. Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer. Journal of Cancer 2021. doi: 10.7150/jca.50370.

2. Yi X, et al. IGFBP7 and the Tumor Immune Landscape: A Novel Target for Immunotherapy in Bladder Cancer. Front. Immunol. 2022. doi: 10.3389/fimmu.2022.898493.

3. CD93 Blockade Stabilizes Tumor Vasculature to Improve Therapy Response. Cancer Discovery (2021) 11(10):2368. doi: 10.1158/2159-8290.Cd-rw2021-113.

4.  Huang X, et al. The Diagnostic Value of Serum IGFBP7 in Patients with Esophageal Squamous Cell Carcinoma. J Cancer 2019, 10(12):2687-2693.

5. Jin L, et al. Insulin Growth Factor Binding Protein 7 (IGFBP7)-Related Cancer and IGFBP3 and IGFBP7 Crosstalk. Frontiers in Oncology, 2020. https://doi.org/10.3389/fonc.2020.00727.

6. Yamanaka Y, et al. Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem. 1997. doi: 10.1074/jbc.272.49.30729.

7. Oh Y., et al. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I -II. J Biol Chem. 1996. doi: 10.1074/jbc.271.48.30322.

8. de Meyts P, et al. Insulin and IGF-I receptor structure and binding mechanism. In: Saltiel AR, Pessin JE, editors.Madame Curie Bioscience Database [Internet]. Austin, TX: Landes Bioscience (2000–2013). Available online at: https://www.ncbi.nlm.nih.gov/books/NBK6192/

9. Li Y, et al. Downregulated IGFBP7 facilitates liver metastasis by modulating epithelial‑mesenchymal transition in colon cancer. Oncol Rep 2019, 42(5):1935-1945.

10. Cai X, et al. Silence of IGFBP7 suppresses apoptosis and epithelial mesenchymal transformation of high glucose induced-podocytes. Exp Ther Med 2018, 16(2):1095-1102.

11. Sun Y, et al. Blockade of the CD93 Pathway Normalizes Tumor Vasculature to Facilitate Drug Delivery and Immunotherapy. Sci Trans Med, 2021. doi: 10.1126/scitranslmed.abc8922.

12. Gao, J.,et al. IGFBP‑rP1 affects the proliferation, apoptosis and macrophage polarization of endometrial cancer cells by regulating the PI3K/AKT pathway. Experimental and Therapeutic Medicine, 2023. https://doi.org/10.3892/etm.2023.11868.

13. Y. Xie, et al., Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury,ssss Kidney International, 2019, doi: 10.1016/j.kint.2019.01.020.

14. Zhang, L., et al. Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure. Nature Cardiovascular Research, 2022. https://doi.org/10.1038/s44161-022-00181-y.

15. Bolomsky, et al. Insulin like growth factor binding protein 7 (IGFBP7) expression is linked to poor prognosis but may protect from bone disease in multiple myeloma. BMC, 2015. https://doi.org/10.1186/s13045-014-0105-1.

16. Smith E, et al. IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation. Br J Cancer, 2014. https://doi.org/10.1038/bjc.2013.783.

17. Qiu, B., et al. Diagnostic Value of Serum Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) in Colorectal Cancer. OncoTargets and therapy, 2020. https://doi.org/10.7717/peerj.15419.

18. National Library of Medicine (U.S.). (n.d.). ClinicalTrials.gov. Retrieved July 14, 2023, from https://clinicaltrials.gov/search?term=IGFBP7.

19. Sun, Y., et al. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine,2021. https://doi.org/10.1126/scitranslmed.abc8922.

20. Yamamoto, K., et al. A top-down approach to uncover the hidden ligandome of low-density lipoprotein receptor-related protein 1 in cartilage. Matrix Biology, 2022. https://doi.org/10.1016/j.matbio.2022.08.007.

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