Role of the stromal microenvironment in carcinogenesis of the prostate
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The topic of this review is the role of stromal-epithelial interactions in normal and malignant prostatic growth. Because cell-cell interactions and androgens play such key roles in the prostate, the goal of this review will be to apply endocrinologic and developmental concepts to the understanding of normal and malignant prostatic growth. Prostatic development is induced by androgens, which act via androgen receptors. Androgens elicit prostatic epithelial growth during fetal and prepubertal periods, and in adulthood androgens act via reciprocal homeostatic stromal-epithelial interactions to maintain functional differentiation and growth quiescence. During carcinogenesis, these reciprocal homeostatic stromal-epithelial interactions are disrupted. In this review, 2 models of prostatic carcinogenesis will be reviewed, both of which emphasize the role of the stromal microenvironment in the carcinogenic process. Hormonal carcinogenesis of the prostate can be elicited by treatment of rats and mice with testosterone plus estradiol (T+E2). Using an immortalized but nontumorigenic human prostatic epithelial cell line (BPH-1), tissue recombinant studies were employed to explore the cellular mechanisms of prostatic carcinogenesis. Accordingly, human BPH-1 prostatic epithelial cells were combined with rat UGM, and the resultant UGM+BPH-1 recombinants were grown in adult male nude mouse hosts. In untreated mouse hosts, UGM+BPH-1 recombinants produced solid branched epithelial cords and ductal structures exhibiting benign growth. In T+E2-treated hosts, UGM+BPH-1 recombinants formed invasive carcinomas. Since BPH-1 cells lack androgen and estrogen receptors, whereas rat UGM expresses both of these receptors, it is proposed that hormonal carcinogenesis is elicited by T+E2 via paracrine mechanisms mediated by the stromal microenvironment. During prostatic carcinogenesis in rats and humans, the periepithelial stroma undergoes progressive loss in smooth muscle with the appearance of carcinoma-associated fibroblasts (CAFs). This abnormal stroma was shown to promote carcinogenesis in genetically abnormal but nontumorigenic epithelial cells. CAF+BPH-1 tissue recombinants grown in male hosts formed carcinomas, whereas benign growth and orderly tissue architecture developed in recombinants composed of normal prostatic stroma+BPH-1. Malignant transformation triggered by CAF was associated with additional genetic alterations and changes in gene expression in the BPH-1 cells. Thus, the stromal microenvironment is a critical determinant of benign versus malignant growth.
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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) | 0.001 | 0.001 |
| 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) | 0.000 | 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 it