ArticleThe Journal of biological chemistry2016
Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 106 citations in OpenAlex.
- Association Between Physical Activity and Mortality in Men with or at Risk of Prostate Cancer: A Systematic Review.Healthcare (Basel, Switzerland) · 2026Review
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Biomimetic bone niche reconstructs proliferation-inhibited and therapy-resistant bone-metastatic prostate cancer.Bioactive materials · 2026Article
- Article
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- Abscisic acid signaling through LANCL2 and PPARγ induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells.Oncology reports · 2024Article
- Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.Clinical and translational medicine · 2024Review
- Review
- Therapy-induced senescent tumor cells in cancer relapse.Journal of the National Cancer Center · 2023Review
- Osteonectin bidirectionally regulates osteoblast mineralization.Journal of orthopaedic surgery and research · 2023Article
- Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.Cancer metastasis reviews · 2023Review
- The genomic regulation of metastatic dormancy.Cancer metastasis reviews · 2023Review
- Adaptive and non-adaptive gene expression responses in prostate cancer during androgen deprivation.PloS one · 2023Article
- Serum starvation-based method of ovarian cancer cell dormancy induction and terminationBiology methods & protocols · 2023Article
- Article
- The extracellular matrix of hematopoietic stem cell niches.Advanced drug delivery reviews · 2022Review
- Thorny ground, rocky soil: Tissue-specific mechanisms of tumor dormancy and relapse.Seminars in cancer biology · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Prostate cancer is known to frequently recur in bone; however, how dormant cells switch its phenotype leading to recurrent tumor remains poorly understood. We have isolated two syngeneic cell lines (indolent and aggressive) through in vivo selection by implanting PC3mm stem-like cells into tibial bones. We found that indolent cells retained the dormant phenotype, whereas aggressive cells grew rapidly in bone in vivo, and the growth rates of both cells in culture were similar, suggesting a role of the tumor microenvironment in the regulation of dormancy and recurrence. Indolent cells were found to secrete a high level of secreted protein acidic and rich in cysteine (SPARC), which significantly stimulated the expression of BMP7 in bone marrow stromal cells. The secreted BMP7 then kept cancer cells in a dormant state by inducing senescence, reducing "stemness," and activating dormancy-associated p38 MAPK signaling and p21 expression in cancer cells. Importantly, we found that SPARC was epigenetically silenced in aggressive cells by promoter methylation, but 5-azacytidine treatment reactivated the expression. Furthermore, high SPARC promoter methylation negatively correlated with disease-free survival of prostate cancer patients. We also found that the COX2 inhibitor NS398 down-regulated DNMTs and increased expression of SPARC, which led to tumor growth suppression in bone in vivo These findings suggest that SPARC plays a key role in maintaining the dormancy of prostate cancer cells in the bone microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.