GEO series

Adrenal-derived factors drive progression of sclerotic prostate cancer in bone

GSE333317 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 48 samples Submitted 2026/05/31 Platform GPL24247Platform GPL24676

Summary

Bone metastasis is a leading cause of death in prostate cancer (PC) patients. Although androgen‐deprivation therapy (ADT) combined with novel androgen‐targeted agents constitutes the cornerstone of systemic treatment, its efficacy is limited. We investigated the adrenal contribution in promoting progression of castration-resistant PC (CRPC) within bone using a preclinical intratibial xenograft model (VCaP, 22Rv1, and LNCaP cells). Mice underwent orchiectomy (ORX) to mimic ADT, with or without adrenalectomy (ORX+ADX) to eliminate adrenal contribution. A significant increase in bone mineral density (BMD) was observed in tumor-grafted tibiae in ORX-treated mice compared to controls (p<0.001), indicating a strong tumor-induced sclerotic response. In contrast, ORX+ADX reduced tumor take rate by approximately 50% and decreased tumor-induced BMD by over 80% (p<0.001). Transcriptomic analysis revealed that ADX downregulated tumor-induced transcripts in bone by over 90%, including osteogenic (Lox, Sparcl1, Bmp2, Postn, Col1a1) and pro-angiogenic (Bmper, Pecam-1, Esam) signatures. Additionally, BMP, PI3K/Akt and ERK1/2 signaling pathways were associated with the tumor-induced bone response. Both high serum progesterone and intratumoral levels of dihydrotestosterone (DHT) were associated with the sclerotic bone phenotype. ADX markedly reduced intratumoral DHT and downregulated glycolytic genes (HK2, PFK2, LDHA) and secretory proteins expressed by the tumor, including Stanniocalcin 2, potentially mediating paracrine effects in the sclerotic bone response. Altogether, these findings highlight the critical role of adrenal- dependent androgen synthesis, particularly via progesterone, in driving the sclerotic CRPC in bone. Our findings suggest that a comprehensive blockade of adrenal contribution is essential to prevent the sclerotic bone response associated with CRPC.

Published in

Adrenal-derived factors drive progression of sclerotic prostate cancer in bone

Hagberg Thulin M, Li L, Abrahamsson S et al. · Endocrine-related cancer 2026 · PMID 42149634 · doi:10.1530/ERC-25-0309

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Direct links to NCBI, no account and no request form: the whole study as GSE333317_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 48 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1470657 and SRA study SRP703816. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42149634) ↗

Study design

40 conditions, each sampled once — no replicated groups

Read from the first 40 of 48 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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