Proteomic and cytokine profiling of a CTRP8-RXFP1 glioma mouse model
Bibliographic record
Abstract
Glioblastoma (GB) is the most prevalent and aggressive primary brain tumor with fatal outcome due to a lack of effective treatments. We previously identified C1q-tumor necrosis factor-related protein 8 (CTRP8), a new member of the adiponectin family, as a novel agonist of the relaxin family peptide receptor 1 (RXFP1) and showed that the CTRP8-RXFP1 ligand-receptor system facilitates increased invasiveness and chemoresistance in GB cells. In the present study, we have investigated the role of the CTRP8-RXFP1 signaling axis in glioma progression using an orthotopic mouse model xenografted with human U251 glioma cells stably expressing CTRP8 and RXFP1. Our results demonstrate that this in-vivo U251-CTRP8/RXFP1 glioma model promoted the formation of aggressive, highly proliferative glioma that resulted in significantly shorter survival times of xenografted mice. CTRP8/RXFP1 xenografts showed strongly elevated mitotic activity, increased expression of cathepsin B at the migrating front and promoted a pro-inflammatory tumor microenvironment characterized by a strong upregulation of cytokines, among them eotaxin-2 and-3, interleukin (IL)-6, IL-18 and others. Proteomic analysis of xenografted mouse brain identified both human and mouse proteome signatures unique to CTRP8/RXFP1 xenografts compared to U251 xenografts. In conclusion, our results suggest that co-expression of CTRP8 and RXFP1 promotes signaling pathways that generate unique tissue proteomic and inflammatory cytokine signatures which promote glioma aggressiveness. The CTRP-RXFP1 signaling pathway may represent an effective therapeutic target for the treatment of fast-progressing and currently untreatable GB.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".