Human SP-D Acts as an Innate Immune Surveillance Molecule Against Androgen-Responsive and Androgen-Resistant Prostate Cancer Cells
Bibliographic record
Abstract
Surfactant Protein D (SP-D), a pattern recognition innate immune molecule, has been implicated in the immune surveillance against cancer. Recently, an association between decreased SP-D expression in human prostate adenocarcinoma and an increased Gleason score and severity has been reported. In the present study, we evaluated the SP-D expression in primary prostate epithelial cells (PrEC) and prostate cancer cell lines. LNCaP, an androgen dependent prostate cancer cell line, exhibited significantly lower mRNA and protein levels of SP-D than PrEC and the androgen-independent cell lines (PC3 and DU145). A recombinant fragment of human SP-D (rfhSP-D), composed of trimeric neck and carbohydrate recognition domains, showed a dose- and time- dependent binding to prostate cancer cells via its CRD region. rfhSP-D induced significantly apoptosis in tumour explants and primary tumor cells isolated from tissue biopsies of metastatic prostate cancer patients. While the viability of PrEC was not altered by rfhSP-D, the rfhSP-D LNCaP (p53+/+) and PC3 (p53-/-) cells showed reduced cell viability in a dose- and time- dependent manner, as they were arrested in G2/M and G1/G0 phase of the cell cycle, respectively. The rfhSP-D treated LNCaP cells showed a significant upregulation of p53 whereas a significant downregulation of pAkt was observed in both PC3 and LNCaP cell lines. The rfhSP-D-induced apoptosis signalling cascade involved upregulation of Bax:Bcl2 ratio, cytochrome c and cleaved products of caspase 7. Thus, rfhSP-D induced apoptosis in prostate tumor explants as well as in androgen-responsive and androgen-resistant prostate cancer cells via p53 and pAkt pathways. Thus, by exploiting multiple apoptotic pathways, rfhSP-D treatment can overcome tumorigenesis of varied forms of prostate cancer.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".