TNFSF12 Human
Description
Biological Functions and Mechanisms
TNFSF12 activates pathways through binding to FN14 and DR3 receptors, influencing:
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Apoptosis: Induces cell death in lymphoma lines via caspase-dependent pathways .
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Angiogenesis: Promotes endothelial cell proliferation (ED50: 2–8 ng/mL in HUVECs) .
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Immune Modulation: Recruits CD8+ T cells, neutrophils, and NK cells in tumor microenvironments .
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Fibrosis: Drives hepatic stellate cell proliferation in chronic liver disease .
Pathway Activation
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NF-κB and TRAF Signaling: Mediates inflammation and survival .
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Epithelial-Mesenchymal Transition (EMT): Enhances metastasis in breast cancer .
Cancer
TNFSF12 exhibits dual roles depending on context:
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Breast Cancer (BRCA): Low expression correlates with poor prognosis (HR = 1.45, p < 0.001), especially in HER2+ subtypes .
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Immune Infiltration: High TNFSF12 levels associate with elevated CD8+ T cells, DCs, and NK cells .
TNFSF12 Expression in Cancers
| Cancer Type | Expression vs. Normal | Prognostic Impact |
|---|---|---|
| Breast (HER2+) | ↓ 2.37 pg/mL | Poor OS, DFS |
| Cervical Squamous | ↓ | Not reported |
| Endometrial | ↔ | Pro-invasive effects |
Non-Cancer Roles
Immune Checkpoint Correlation
High TNFSF12 expression in BRCA correlates with elevated checkpoint genes:
| Checkpoint Marker | Expression Trend | Immunotherapy Implication |
|---|---|---|
| CD276 (B7-H3) | ↑ | Enhanced response |
| TNFRSF25 | ↑ | Potential target |
Drug Sensitivity
Neutralization Studies
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Anti-TNFSF12 antibodies inhibit HT-29 colon cancer proliferation (ND50: 2–8 µg/mL) .
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Recombinant TNFSF12 (1090-TW) suppresses NF-κB in MDA-MB-231 breast cancer cells .
Targeting TNFSF12 Pathways
Product Specs
Recombinant Human TNFSF12 (amino acids 94-249) produced in E. coli results in a single, non-glycosylated polypeptide chain. With a molecular mass of 18 kDa, it comprises 156 amino acids. An 8-amino acid histidine tag (M-HHHHHH-R) is fused to the N-terminus, resulting in a total of 164 amino acids. Purification is achieved using proprietary chromatographic techniques.
The protein is lyophilized from a 0.2 µm filtered solution in phosphate-buffered saline (PBS).
For reconstitution, it is recommended to dissolve the lyophilized TNFSF12 in sterile 18 MΩ-cm H2O to a concentration of at least 100 µg/ml. Further dilutions can be made in other aqueous solutions.
Lyophilized TNFSF12 remains stable at room temperature for up to 3 weeks. However, it is recommended to store the desiccated product at a temperature below -18°C. After reconstitution, TWEAK should be stored at 4°C for 2-7 days. For long-term storage, keep it at -18°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freeze-thaw cycles.
Purity is determined to be greater than 95% using SDS-PAGE analysis.
The half-maximal effective concentration (ED50) is less than 8 ng/ml as measured by a proliferation assay using human umbilical vein endothelial cells (HUVECs).
Escherichia coli.
MHHHHHHRSA PKGRKTRARR AIAAHYEVHP RPGQDGAQAG VDGTVSGWEE ARINSSSPLR YNRQIGEFIV TRAGLYYLYC QVHFDEGKAV YLKLDLLVDG VLALRCLEEF SATAASSLGP QLRLCQVSGL LALRPGSSLR IRTLPWAHLK AAPFLTYFGL FQVH.
Product Science Overview
TNFSF12 exists in both membrane-bound and secreted forms. The membrane-bound form is a type II transmembrane protein, while the secreted form is generated through proteolytic cleavage. The protein structure includes a TNF homology domain, which is crucial for its interaction with the FN14 receptor .
TNFSF12 has a wide range of biological functions, including:
- Induction of Apoptosis: TNFSF12 can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This makes it a significant player in regulating cell death and survival .
- Angiogenesis: It promotes the proliferation and migration of endothelial cells, acting as a regulator of angiogenesis. This function is essential for the formation of new blood vessels .
- Immune Response: TNFSF12 has overlapping signaling functions with TNF but displays a much wider tissue distribution. It plays a role in immune responses, inflammation, and tissue regeneration .
TNFSF12 is involved in various pathological conditions, including:
- Cancer: Its ability to induce apoptosis makes it a potential target for cancer therapy. However, its role in promoting angiogenesis can also contribute to tumor growth and metastasis .
- Inflammatory Diseases: Due to its involvement in immune responses, TNFSF12 is implicated in inflammatory diseases such as rheumatoid arthritis and multiple sclerosis .
- Cardiovascular Diseases: Its role in angiogenesis and endothelial cell function links it to cardiovascular diseases .
Research on TNFSF12 is ongoing to explore its therapeutic potential. The recombinant form of TNFSF12 is used in various experimental settings to study its effects on cell death, angiogenesis, and immune responses. Understanding the precise mechanisms of TNFSF12 signaling can lead to the development of targeted therapies for diseases where TNFSF12 plays a critical role .
