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Cyclin A1 and P450 ...
Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow
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- Miftakhova, Regina R. (author)
- Lund University,Lunds universitet,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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- Hedblom, Andreas (author)
- Lund University,Lunds universitet,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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- Semenas, Julius (author)
- Lund University,Lunds universitet,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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- Robinson, Brian (author)
- Cornell University
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- Simoulis, Athanasios (author)
- Skåne University Hospital
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- Malm, Johan (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Rizvanov, Albert (author)
- Kazan Federal University
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- Heery, David M. (author)
- University of Nottingham
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- Mongan, Nigel P. (author)
- University of Nottingham
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- Maitland, Norman J. (author)
- University of York
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- Allegrucci, Cinzia (author)
- University of Nottingham
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- Persson, Jenny L. (author)
- Lund University,Lunds universitet,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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(creator_code:org_t)
- American Association for Cancer Research (AACR), 2016
- 2016
- English.
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In: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 76:8, s. 2453-2464
- Related links:
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase(CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDHhigh subpopulation of PC3M cells, one model of prostate cancer, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colony forming assays. In the bone marrow, cyclin A1 and aromatase enhanced local bonemarrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted the metastatic growth of prostate cancer cells. Moreover, ALDHhigh tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired agrowth advantage in the presence of host bone marrow cells.Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDHhigh prostate cancer cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Miftakhova, Regi ...
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Hedblom, Andreas
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Semenas, Julius
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Robinson, Brian
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Simoulis, Athana ...
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Malm, Johan
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show more...
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Rizvanov, Albert
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Heery, David M.
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Mongan, Nigel P.
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Maitland, Norman ...
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Allegrucci, Cinz ...
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Persson, Jenny L ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Umeå University
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Lund University