Abstract 5229: Expression and regulation of chondroitin sulfate in prostate cancer
Bibliographic record
Abstract
Abstract Increased levels of chondroitin sulfate (CS) glycosaminoglycans (GAGs) in prostate cancer (PC) have been observed for more than three decades. In 1984, De Klerk et al. noted that hyperplastic and cancerous prostate contained elevated levels of CS while other GAGs, like heparin sulfate (HS), were decreased. Chondroitin sulfate-modified proteoglycans (CSPGs), such as versican or tomoregulin (TENB2), have been promoted as PC progression markers. They have been associated with cell attachment to the matrix, the metastatic phenotype, disease progression, and androgen independence. Functionally, pericellular enrichment of CSPGs in the PC microenvironment promotes cell motility. Our team has discovered that human tumors display high levels of a specific highly sulfate type of CS normally restricted to placental and fetal tissue compartment. This "oncofetal" CS (ofCS) GAG can be conveniently detected and targeted using recombinant CS-binding VAR2CSA (rVAR2) lectins, derived from the malaria parasite Plasmodium falciparum. Recently, we identified chondroitin sulfate biosynthesis as being controlled by androgens in PC, modulating expression of the CHST11 and CHST13 carbon-4 GalNAc sulfotransferases. We established that these enzymes are under direct control of the androgen receptor (AR), regulating synthesis of the cancer-associated ofCS-modification on CSPGs. Glycosylation has a key role in many important biologic processes in cancer including cell differentiation. We identified CHST11 to be highly increased in high-risk neuroendocrine prostate cancer (NEPC) both in vitro, in vivo, and in situ. Moreover, cells that expressed neuroendocrine markers showed higher level of sulfation and ofCS. Our work reveals that alterations in GAG signatures regulated by AR might be responsible for progression neuroendocrine differentiation in prostate cancer. The prostate is an abundant secretor of PGs, and tumor-specific alterations in GAG signatures such as ofCS therefore constitute an untapped reservoir of potential biomarkers to be exploited as therapeutic targets. Citation Format: Nader Al Nakouzi, Chris Kedong Wang, Irina Nelepcu, Coralie Crouzit, Noushin Nabavi, Amal Almami, Htoo Zarni Oo, Thomas Mandel Clausen, Tobias Gustavsson, Ali Salanti, Mads Daugaard. Expression and regulation of chondroitin sulfate in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5229.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".