Abstract 716: CXCR4 antagonist, CTCE-9908, inhibits PC-3 cell invasiveness and metastasis
Bibliographic record
Abstract
Abstract Chemokines and their receptors function in the migration and homing of cells to target tissues. Current evidence suggests that cancer cells activate chemokines and their receptors during dissemination and metastasis formation at secondary sites. Previously, in prostate cancer cells, we showed that binding of the chemokine CXCL12 to its receptor CXCR4 induced signaling events leading to MMP-9 expression, migration and invasion. CXCL12/CXCR4 transactivation of epidermal growth factor family receptors in lipid raft membrane microdomains on cell surface mediates these invasive signaling events and subsequent expansion of the skeletal metastatic deposits. Herein, we tested the efficacy of CXCR4 antagonist CTCE-9908 in prostate cancer cell growth, invasion, and metastasis. Methods: We used in vitro growth and invasion assays and in vivo orthotopic model system to asses the tumor growth and metastasis. Results: We found that (a) CTCE-9908 treatment resulted in no significant change in the growth of PC-3 cells; (b) CTCE-9908 compound at 50 μg/ml inhibited CXCL12 mediated invasion of PC-3 cells; (c) in vivo CTCE-9908 compound did not significantly altered the growth of primary tumors as measured by calipers and (d) the total tumor burden in the animal including the growth of prostate and soft tissue metastases to lymph node and distant organ tissues were significantly decreased upon CTCE-9908 administration. Histological analysis showed that CTCE-9908 treatment resulted in tumor necrosis in primary prostate tumors. Conclusions: These data suggest that CXCR4 inhibition by CTCE-9908 compound decreased the invasive signaling and metastatic spread of tumor cells without apparently affecting the primary tumor growth in animal model. Hence, CTCE-9908 is an efficacious antagonist for CXCL12/CXCR4 signaling pathway mediating invasive spread of tumor cells in secondary metastasis formation. Studies of CTCE-9908 in phase II are planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 716.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".