Abstract 55: Separation of tetraspanin CD151 from its integrin partner α3β1 reflects an alter migratory state and predicts prostate cancer progression
Bibliographic record
Abstract
Abstract The dysregulation of cell migration enables tumor cells to escape their tissue of origin and disseminate. Since cancer-related deaths are primarily caused by the dissemination of tumor cells, mechanisms of migration are both a target for therapy and an indicator of disease progression. The regulation of cell adhesion is widely recognized as a rate-limiting step in metastasis but how tumor cells achieve dynamic control over their adhesion receptors is poorly understood. During an analysis of prostate cancer progression we discovered that α3β1 expression is reduced and that its tetraspanin partner, CD151, is not “integrin-free”. We were able to detect integrin-free CD151 using antibodies specific to the integrin-binding domain of CD151. Dual staining of tumor tissue and normal tissue from prostate cancer patients for total CD151 and integrin-free CD151 revealed that the appearance of integrin-free CD151 corresponds with poor-patient outcome. In fact, the detection of integrin-free CD151 is an independent predictor of prostate cancer progression. Surprisingly, the clustering of integrin-free CD151 immobilizes tumor cells in vivo and prevents metastasis suggesting that the ability of CD151 to control migration does not depend on its α3β1 integrin partner. Indeed, integrin-free CD151 is now associated with non-integrin partners through which it can regulate tumor cell motility. These observations demonstrate that the appearance of integrin-free CD151 reflects the disruption of the CD151/ α3β1/laminin axis and thereby reveals an altered migratory ability in tumor cells. This has clinical as well molecular implications. Integrin-free CD151 can be used as a molecular indicator of disease progression and assist in the distinction between indolent (benign) and advanced disease (Palmer et al. 2013). In addition, the identification of new CD151 partners can provide new therapeutic targets to inhibit the motility of tumor cells that have undergone this change in migratory status. A preliminary evaluation identified a similar appearance of integrin-free CD151 in cancers derived from other tissues, suggesting that this change in molecular status is broadly applicable to most solid tumors. Palmer, et al. (2013). Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Research. Citation Format: Trenis Palmer, Carlos Martinez, Catalina Vasquez, Katie Hebron, Shanna Arnold, Celestial Jones-Paris, Susanne Chan, Venu Chalasani, Jose Gomez-Lemus, Andrew Williams, Joseph Chin, Giovanna Giannico, Tatiana Ketova, John Lewis, Andries Zijlstra. Separation of tetraspanin CD151 from its integrin partner α3β1 reflects an alter migratory state and predicts prostate cancer progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 55. doi:10.1158/1538-7445.AM2014-55
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".