C1QTNF8 (Complement C1q Tumor Necrosis Factor-Related Protein 8), also known as CTRP8, is a secreted protein belonging to the C1q/TNF superfamily. It plays roles in immune regulation, metabolism, and cancer biology. This protein is expressed as a 252–255 amino acid polypeptide (28.4 kDa) and is produced recombinantly in Escherichia coli for research purposes .
Gene/Protein Detail | Information |
---|---|
Official Symbol | C1QTNF8 |
Chromosome | 16 (GRCh38) |
Gene ID | 390664 |
Alternative Names | CTRP8, UNQ5829, C1q/TNF-related protein 8 |
C1QTNF8 is encoded by a single gene on chromosome 16, with evidence of protein existence confirmed by UniProt .
In prostate cancer, C1QTNF8+ mast cells correlate with biochemical recurrence, suggesting a role in tumor progression .
C1QTNF8 binds to RXFP1 (relaxin family peptide receptor 1), modulating immune and oncogenic pathways:
Mast Cell Regulation:
Cancer Progression:
Method | Tool | Application |
---|---|---|
Immunohistochemistry | Anti-C1QTNF8 polyclonal antibody | Tissue staining, cancer biomarker studies |
Western Blot | Recombinant C1QTNF8 (e.g., PROTP60827) | Protein validation, signaling studies |
Functional Assays | RXFP1 agonist/antagonist co-treatment | Mechanistic studies in mast cells/cancer |
Recombinant C1QTNF8 is critical for validating antibodies and studying RXFP1-dependent pathways .
Methodological guidance:
Immunohistochemistry (IHC): Use validated antibodies targeting the C1q globular domain (e.g., clone 3F12) with antigen retrieval in formalin-fixed paraffin-embedded tissues. Include mast cell tryptase co-staining (e.g., anti-tryptase MCA2377GA) to identify prostate cancer-associated MCT subpopulations .
ELISA: Commercial kits (e.g., Human CTRP8/CTRF8 ELISA, SEB945Hu) require pre-analytical validation for serum/plasma matrix effects. Detectable range: 0.1–60 ng/mL .
Western blot: Recombinant C1QTNF8 migrates at ~28.4 kDa under non-reducing conditions. Use Tris-Tricine gels for improved resolution .
Key findings:
Methodological note: Stratify analyses by mast cell subtype (MCT vs MCTC) using chymase co-staining .
Conflict: Studies report both pro-tumorigenic (via RXFP1-JAK3-STAT3 axis in glioblastoma ) and tumor-suppressive effects (in prostate cancer microenvironment ).
Resolution framework:
Structural challenges: The C1q domain forms pH-sensitive trimers requiring:
Functional validation: Combine:
Therapeutic candidates:
Preclinical validation pipeline:
Inter-assay variability:
Platform | Dynamic Range | Cross-reactivity |
---|---|---|
Luminex xMAP | 0.5–200 ng/mL | CTRP9 (12%) |
MSD-ECL | 0.1–100 ng/mL | CTRP3 (8%) |
Complement C1q Tumor Necrosis Factor-Related Protein 8 (CTRP8) is a member of the C1q/TNF-related protein (CTRP) family. This family consists of secreted proteins that play significant roles in various physiological processes, including metabolism, inflammation, and cancer. CTRP8, like other members of the CTRP family, is characterized by its structural domains, which include an N-terminal variable domain, a stalk region, and a C-terminal trimerizing globular C1q (gC1q) domain .
CTRP8 is known for its ability to form homo- and heterotypic trimers and oligomers, which can exhibit different biological activities. The gC1q domain is crucial for the trimerization and function of these proteins. The structure of CTRP8 allows it to interact with specific receptors and activate downstream signaling pathways .
One of the key receptors for CTRP8 is the relaxin family peptide receptor 1 (RXFP1). The interaction between CTRP8 and RXFP1 has been shown to activate several signaling pathways that support enhanced cell motility and survival. This interaction is particularly significant in the context of cancer, where CTRP8 has been identified as a novel ligand of RXFP1 with functions in brain cancer .
CTRP8 has emerged as an important player in cancer biology. It has been implicated in the promotion of tumor growth and tissue invasion. In glioblastoma, a type of brain cancer, CTRP8 has been shown to enhance cell migration and survival through its interaction with RXFP1. This makes CTRP8 a potential therapeutic target for cancer treatment .
Beyond its role in cancer, CTRP8, along with other CTRP family members, is involved in the regulation of metabolism and inflammation. CTRPs have been shown to have anti-inflammatory and insulin-sensitizing effects, making them relevant in conditions such as obesity, type 2 diabetes, coronary artery disease, and non-alcoholic fatty liver disease (NAFLD). The coordinated communication of different organs mediated by CTRPs is essential for maintaining a healthy metabolic state .