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出抑制或促進腫瘤生長的“自相矛盾”活性。研究發現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。
01 IGFBP7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:doi.org/10.3389/fonc.2020.00727)
02 IGFBP7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。
03 IGFBP7在研究中的應用
IGFBP7蛋白和抗體用于研究腫瘤微環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HEK 293T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,結果發現IGFBP7在腫瘤脈管系統中表達上調。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,結果發現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
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明星產品 | |||
貨號 | 種屬 | 標簽 | 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
【參考文獻】
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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. 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: ncbi.nlm.nih.gov/books/NBK6192/
9. Li Y, et al. Downregulated IGFBP7 facilitates liver metastasis by modulating epithelialmesenchymal 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. IGFBPrP1 affects the proliferation, apoptosis and macrophage polarization of endometrial cancer cells by regulating the PI3K/AKT pathway. Experimental and Therapeutic Medicine, 2023. 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.
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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. 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. 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. doi.org/10.7717/peerj.15419.
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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. doi.org/10.1016/j.matbio.2022.08.007.
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