Application of Angiopoietin 2 (ANGPT2) in Tumors-Special topic on antibody modification-Tekbiotech-Yeast Display Service,Phage display technology

Application of Angiopoietin 2 (ANGPT2) in Tumors

Introduction to Angiopoietin 2

Angiopoietin (ANGPT) can regulate angiogenesis by binding to the tyrosine kinase receptor TIE2 on endothelial cells. Angiopoietin family members include angiopoietin 1 (ANGPT1), angiopoietin 2 (ANGPT2), angiopoietin 3 (ANGPT3), and angiopoietin 4 (ANGPT4). Angpt1 is an agonist for TIE2. ANGPT2 was identified by cDNA library screening shortly after the identification of angiopoietin-1 (Ang1). Angpt2 has 60% homology with Ang1, but has the opposite function of Angpt1.

ANGPT2 protein contains 496 amino acids, with a secretory signal peptide, a coiled-coil domain, and a fibrin domain. Angpt2 protein promotes tumor cell growth in an autocrine and paracrine manner. In certain specific situations (inflammation, hypoxia, cancer, etc.), the expression level of Angpt2 is high. In addition, high concentrations of Angpt2 lacking Angpt1 can act as a TIE2 agonist.

ANGPT2 is a secreted factor in the angiopoietin/Tie (tyrosine kinase with Ig and EGF homology domains) signaling pathway and is associated with vascular diseases. Studies have shown that ANGPT2 plays a key role in angiogenesis and can increase or decrease angiogenesis. ANGPT2 expression is associated with microvessel density, tumor size, and metastatic efficacy, indicating that ANGPT2 is a major factor in the progression of multiple cancer types. The latest research found that inhibition of ANGPT2 can restore vascular stability, thereby inhibiting tumor angiogenesis and reducing the metastasis of early and even late malignant tumors.

Angiopoietin 2 and Tumors

Tumors are generated by the interaction of cellular and non-cellular factors in the tumor microenvironment, among which endothelial cells are an important factor in angiogenesis. A large number of studies have shown that the expression of Angpt2 is significantly upregulated in gastrointestinal pancreatic cancer, ovarian cancer, and malignant melanoma.

Application of Angiopoietin 2 in Tumors

ANGPT2 is used as a biomarker for different cancer types. Therefore, the ANGPT2 target has attracted much attention, and ANGPT2 antibodies based on the ANGPT2 target have gradually emerged.

-- In breast cancer models, the use of ANGPT2 and VEGF growth factors was effective in reducing the metastatic rate of lesions.

-- ANGPT2 overexpression accelerated metastasis to lymph nodes and lungs, while ANGPT2 antibodies inhibited tumor cell metastasis to lymph nodes and lungs in addition to blocking lymphangiogenesis.

-- In patients with hepatocellular carcinoma, ANGPT2 levels were upregulated in the liver; after treatment, ANGPT2 levels decreased.

-- In metastatic MMTV-PyMT breast cancer and RIP1-Tag2 pancreatic insulinoma, ANGPT2 inhibition reduced Tie2 in macrophages and angiogenesis.

Studies have shown that ANGPT2 can induce EMT in cancer. ANGPT2 expression was increased in lung cancer cell lines, and knockout inhibited the EMT process. Similarly, blocking ANGPT2 expression in cervical cancer cells reduced vimentin expression and microvessel density, demonstrating its role in EMT and ultimately cancer metastasis.

Treatment Cases of Angiopoietin 2

Studies have found that PitNET cells express TIE2 receptors and secrete ANGPT2, and ANGPT2 in tumor cells stimulates TIE2 to activate downstream cell proliferation signals. Tie2 gene deletion inhibits the growth of PitNETs in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signals can antagonize PitNETs in primary cell culture, mouse tumor transplantation, and MENX rats.

Expression of ANGPT2-tekbiotech.jpeg

Fig.1 Expression of ANGPT2

Studies have found that MYBL1 enhances ANGPT2 expression by directly targeting the ANGPT2 promoter and transcriptionally upregulates ANGPT2 mRNA expression by interacting with PRMT5, MEP50, and WDR5. Therefore, MYBL1 plays a carcinogenic role in HCC angiogenesis and sorafenib resistance.

Fig.2 MYBL1 induces transcriptional expression of ANGPT2 to promote tumor angiogenesis

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