Bone stromal production of insulin-like growth factor binding protein 5 promotes growth and survival of prostate cancer
Bibliographic record
Abstract
Prostate cancer (PCa) is the most common cancer among Canadian men and is continuing to be the third-leading cause of male cancer death in Canada. PCa is initially androgen-dependent. Some patients developed metastasis at diagnosis, and are treated by androgen withdrawal therapy. The majority of patients will respond, resulting in tumor growth arrest. However, PCa eventually progresses to androgen-independence and no effective treatment is available. Stromal-epithelial interaction is critical to PCa survival and proliferation. The bone metastasis in PCa indicated compatibility between bone stroma cells and PCa epithelial cells in bone microenvironment. IGF-I and IGF-II are the most abundant growth factors stored in bone. The bioavailability of lGF-I can be modulated by IGFBP-5, the most abundant IGFBP in bone stroma. IGFBP-5 is one of few consistently upregulated genes in mice bone stroma after castration. The functions of IGFs and IGFBP-5 are implicated in PCa growth and survival. The objective of this thesis was to investigate the role of stroma-derived IGFBP-5 in PCa bone metastasis and progression to androgen-independence. We generated IGFBP-5 expressing bone stroma MG63-BP5 clone, and its vector counterpart MG63-mock clone. We investigated the anti-apoptotic effect of MG63-BP5 conditioned medium on LNCaP PCa cells under androgen-deprived condition through enhancing IGF-I-mediated survival signaling. We observed the ability of MG63 cells to support LNCaP tumor formation in nude mice coinoculated with LNCaP/MG63 cells. We also observed an increase in growth rate and PSA level in LNCaP/MG63-BP5 xenografts compared to LNCaP/MG63-mock xenografts both in intact and castrated mice. Immunohistochemical staining of these xenografts showed no difference in proliferation, however decreased apoptosis was seen in LNCaP/MG63-BP5 xenografts. Our study is the first to demonstrate that bone stroma-produced paracrine IGFBP-5 played a role in bone microenvironment that favors PCa cell survival as well as androgen-independent progression. We propose that IGFBP-5 can act as a reservoir for IGF-I that allows slowly release of IGF-I for receptor interactions, resulting in amplification of downstream signaling pathways, which promote cell survival. We concluded that this is an adaptive mechanism for PCa to resist undergoing apoptosis and survive under androgen deprivation stress.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 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".