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Halin Bergström, Sofia
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Publications (10 of 22) Show all publications
Adamo, H. H., Hammarsten, P., Hägglöf, C., Scherdin, T. D., Egevad, L., Stattin, P., . . . Bergh, A. (2019). Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome. The Prostate, 79(5)
Open this publication in new window or tab >>Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
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2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 5Article in journal (Refereed) Published
Abstract [en]

Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
biomarkers, C, EBP, prostate cancer, tumors instruct adjacent tissues
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-157947 (URN)10.1002/pros.23749 (DOI)000461573200001 ()30536410 (PubMedID)
Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17Bibliographically approved
Halin Bergström, S., Järemo, H., Nilsson, M., Adamo, H. H. & Bergh, A. (2018). Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness. The Prostate, 78(4), 257-265
Open this publication in new window or tab >>Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness
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2018 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 4, p. 257-265Article in journal (Refereed) Published
Abstract [en]

Background: Microseminoprotein-beta (MSMB) is a major secretory product from prostate epithelial cells. MSMB synthesis is decreased in prostate tumors in relation to tumor grade. MSMB levels are also reduced in the circulation and MSMB is therefore used as a serum biomarker for prostate cancer. We hypothesized that cancers induce a reduction in MSMB synthesis also in the benign parts of the prostate, and that the magnitude of this response is related to tumor aggressiveness. Reduced levels of MSMB in the circulation could therefore be a consequence of reduced MSMB expression not only in tumor tissue but also in the benign prostate tissue.

Methods: MSMB expression was analyzed in prostatectomy specimens from 36 patients using immunohistochemistry and qRT-PCR. MSMB expression in the benign prostate tissue was analyzed in relation to Gleason score, tumor stage, and distance to the tumor. Furthermore, Dunning rat prostate tumors with different aggressiveness were implanted into the prostate of Copenhagen rats to study if this affected the MSMB expression in the tumor-adjacent benign rat prostate tissue.

Results: In prostatectomy specimens, MSMB expression was reduced in prostate tumors but also in the tumor-adjacent benign parts of the prostate. The reduction in tumor MSMB was related to tumor grade and stage, and the reduction in the benign parts of the prostate to tumor grade, stage, and distance to the tumor. Implantation of Dunning cancer cells into the rat prostate resulted in reduced MSMB protein levels in the tumor-adjacent benign prostate tissue. Rapidly growing and metastatic MatLyLu tumors had a more pronounced effect than slow-growing non-metastatic G tumors.

Conclusion: Our data suggest that aggressive prostate tumors suppress MSMB synthesis in the benign prostate and that this could explain why serum levels of MSMB are decreased in prostate cancer patients. This study suggests that markers for aggressive cancer can be found among factors altered in parallel in prostate tumors and in the adjacent benign tissue.

Keywords
beta-inhibin, Dunning rat prostate tumors, PSP94, TINT, tumor-adjacent benign prostate tissue, tumor-instructed normal tissue
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-144815 (URN)10.1002/pros.23466 (DOI)000423474900003 ()29250809 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-06-09Bibliographically approved
Strömvall, K., Thysell, E., Halin Bergström, S. & Bergh, A. (2017). Aggressive rat prostate tumors reprogram the benign parts of the prostate and regional lymph nodes prior to metastasis. PLoS ONE, 12(5), Article ID e0176679.
Open this publication in new window or tab >>Aggressive rat prostate tumors reprogram the benign parts of the prostate and regional lymph nodes prior to metastasis
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176679Article in journal (Refereed) Published
Abstract [en]

In order to grow and spread tumors need to interact with adjacent tissues. We therefore hypothesized that small but aggressive prostate cancers influence the rest of the prostate and regional lymph nodes differently than tumors that are more indolent. Poorly metastatic (Dunning AT1) or highly metastatic (Dunning MLL) rat prostate tumor cells were injected into the ventral prostate lobe of immunocompetent rats. After 10 days-when the tumors occupied about 30% of the prostate lobe and lymph node metastases were undetectable- the global gene expression in tumors, benign parts of the prostate, and regional iliac lymph nodes were examined to define tumor-induced changes related to preparation for future metastasis. The tumors induced profound effects on the gene expression profiles in the benign parts of the prostate and these were strikingly different in the two tumor models. Gene ontology enrichment analysis suggested that tumors with high metastatic capacity were more successful than less metastatic tumors in inducing tumor-promoting changes and suppressing anti-tumor immune responses in the entire prostate. Some of these differences such as altered angiogenesis, nerve density, accumulation of T-cells and macrophages were verified by immunohistochemistry. Gene expression alterations in the regional lymph nodes suggested decreased quantity and activation of immune cells in MLL-lymph nodes that were also verified by immunostaining. In summary, even when small highly metastatic prostate tumors can affect the entire tumor-bearing organ and pre-metastatic lymph nodes differently than less metastatic tumors. When the kinetics of these extratumoral influences (by us named TINT = tumor instructed normal tissue) are more precisely defined they could potentially be used as markers of disease aggressiveness and become therapeutic targets.

Place, publisher, year, edition, pages
Public library science, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-135971 (URN)10.1371/journal.pone.0176679 (DOI)000400648500061 ()28472073 (PubMedID)
Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2018-06-09Bibliographically approved
Strömvall, K., Lundholm, M., Thysell, E., Bergh, A. & Halin Bergström, S. (2017). Highly aggressive rat prostate tumors rapidly precondition regional lymph nodes for subsequent metastatic growth. PLoS ONE, 12(10), Article ID e0187086.
Open this publication in new window or tab >>Highly aggressive rat prostate tumors rapidly precondition regional lymph nodes for subsequent metastatic growth
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0187086Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to examine in what ways MatLyLu (MLL) rat prostate tumors with high metastatic capacity influence regional lymph nodes prior to metastatic establishment compared to AT1 rat prostate tumors with low metastatic potential. MLL or AT1 tumor cells were injected into the ventral prostate of immunocompetent rats. Tumor and lymph node morphology, and lymph node mRNA expression of macrophage associated markers, T-cell associated markers, and cytokines were examined over time until the first microscopic signs of metastases (at day 14 for MLL- and at day 28 for AT1-tumors). Already at day 3 after tumor cell injection, when the tumors were extremely small and occupied less than 1% of the prostate volume, MLL- and AT1-tumors provoked different immune responses in both the prostate and the regional lymph nodes. MLL-tumors induced expression of immunosuppressive cytokines, suppressed T-cell accumulation, and directed T-cells towards an immunosuppressive phenotype. AT1-tumors caused a response more similar to that in vehicle-injected animals, with accumulation of T-cells in tumors and regional lymph nodes. Prostate tumors with high metastatic potential were able to precondition regional lymph nodes to subsequent metastatic growth in ways different from tumors with less metastatic potential. This may indicate the existence of a time-window when pre-metastatic changes in regional lymph nodes can aid in the prognostication of locally aggressive and potentially metastatic prostate cancer.

Place, publisher, year, edition, pages
San Fransisco: Public Library of Science (PLoS), 2017
Keywords
Prostate cancer, tumor instructed normal tissue, TINT, non-malignant prostate tissue, lymph nodes, lymph node metastasis, pre-metastatic niche, tumor microenvironment, tumor macroenvironment, Dunning rat model of prostate cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-140152 (URN)10.1371/journal.pone.0187086 (DOI)000413845400110 ()29073272 (PubMedID)
Note

Originally included in thesis in manuscript form.

Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-06-09Bibliographically approved
Nordstrand, A., Halin Bergström, S., Thysell, E., Bovinder-Ylitalo, E., Lerner, U. H., Widmark, A., . . . Wikström, P. (2017). Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects of castration in a rat model for prostate cancer growth in bone. Clinical and Experimental Metastasis, 34(3-4), 261-271
Open this publication in new window or tab >>Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects of castration in a rat model for prostate cancer growth in bone
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2017 (English)In: Clinical and Experimental Metastasis, ISSN 0262-0898, E-ISSN 1573-7276, Vol. 34, no 3-4, p. 261-271Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PCa) patients with bone metastases are primarily treated with androgen deprivation therapy (ADT). Less pronounced ADT effects are seen in metastases than in primary tumors. To test if acute effects of ADT was enhanced by concurrent inhibition of pro-survival insulin-like growth factor 1 (IGF-1), rats were inoculated with Dunning R3327-G tumor cells into the tibial bone marrow cavity and established tumors were treated with castration in combination with IGF-1 receptor (IGF-1R) inhibitor NVP-AEW541, or by each treatment alone. Dunning R3327-G cells were stimulated by androgens and IGF-1 in vitro. In rat tibia, Dunning R3327-G cells induced bone remodeling, identified through increased immunoreactivity of osteoblast and osteoclast markers. Tumor cells occasionally grew outside the tibia, and proliferation and apoptotic rates a few days after treatment were evaluated by scoring BrdU- and caspase-3-positive tumor cells inside and outside the bone marrow cavity, separately. Apoptosis was significantly induced outside, but unaffected inside, the tibial bone by either castration or NVP-AEW541, and the maximum increase (2.7-fold) was obtained by the combined treatment. Proliferation was significantly reduced by NVP-AEW541, independently of growth site, although the maximum decrease (24%) was observed when NVP-AEW541 was combined with castration. Tumor cell IGF-1R immunoreactivity was evaluated in clinical PCa bone metastases (n = 61), and positive staining was observed in most cases (74%). In conclusion, IGF-1R inhibition may be evaluated in combination with ADT in patients with metastatic PCa, or in combination with therapies for the subsequent development of castration-resistant disease, although diverse responses could be anticipated depending on metastasis site.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Bone metastasis, IGF-1R, Apoptosis, Proliferation, Immune response, RUNX2, TRAP
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-131804 (URN)10.1007/s10585-017-9848-8 (DOI)000401996600008 ()28447314 (PubMedID)
Note

Special Issue.

Originally published in thesis in manuscript form.

Available from: 2017-02-22 Created: 2017-02-22 Last updated: 2019-05-20Bibliographically approved
Strömvall, K., Sundkvist, K., Ljungberg, B., Halin Bergström, S. & Bergh, A. (2017). Reduced number of CD169(+) macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients. The Prostate, 77(15), 1468-1477
Open this publication in new window or tab >>Reduced number of CD169(+) macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients
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2017 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 15, p. 1468-1477Article in journal (Refereed) Published
Abstract [en]

Background: Tumor-derived antigens are captured by CD169+ (SIGLEC1+) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti-tumor immune response. Reduced CD169 expression in pre-metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.

Methods: CD169 expression was measured with immunohistochemistry in metastasis-free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA-relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan-Meier survival- and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre-metastatic LNs draining either highly metastatic MatLyLu- or poorly metastatic AT1-tumors.

Results: In patients with low CD169 immunostaining in metastasis-free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining (P < 0.001). CD169 expression in regional LNs was not associated with PSA-relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre-metastatic regional LNs compared with rats with poorly metastatic tumors.

Conclusion: Low expression of CD169 in metastasis-free regional LNs indicates a reduced anti-tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
Dunning rat prostate tumors, SIGLEC1, immunohistochemistry, prostate cancer death, tumor-draining lymph nodes
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-140105 (URN)10.1002/pros.23407 (DOI)000412676200002 ()28880401 (PubMedID)
Available from: 2017-09-29 Created: 2017-09-29 Last updated: 2018-06-09Bibliographically approved
Halin Bergström, S., Hägglöf, C., Thysell, E., Bergh, A., Wikström, P. & Lundholm, M. (2016). Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth. Scientific Reports, 6, Article ID 31805.
Open this publication in new window or tab >>Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 31805Article in journal (Refereed) Published
Abstract [en]

Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-125538 (URN)10.1038/srep31805 (DOI)000381757500001 ()
Available from: 2016-09-19 Created: 2016-09-13 Last updated: 2018-06-07Bibliographically approved
Halin Bergström, S., Nilsson, M., Adamo, H., Thysell, E., Jernberg, E., Stattin, P., . . . Bergh, A. (2016). Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth. PLoS ONE, 11(6), Article ID e0157280.
Open this publication in new window or tab >>Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0157280Article in journal (Refereed) Published
Abstract [en]

Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RTPCR showed that the main site of HO-1 synthesis was HO-1(+) macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1(+) macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1(+) macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1(+) macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1(+) macrophages may have an important role in prostate cancer.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-123975 (URN)10.1371/journal.pone.0157280 (DOI)000377563000117 ()
Available from: 2016-11-15 Created: 2016-07-07 Last updated: 2018-06-09Bibliographically approved
Nilsson, M., Adamo, H., Bergh, A. & Halin Bergström, S. (2016). Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer. Scientific Reports, 6, Article ID 19608.
Open this publication in new window or tab >>Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19608Article in journal (Refereed) Published
Abstract [en]

Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.

National Category
Cancer and Oncology Medical Bioscience
Identifiers
urn:nbn:se:umu:diva-130005 (URN)10.1038/srep19608 (DOI)000368816300001 ()26804196 (PubMedID)
Available from: 2017-01-12 Created: 2017-01-11 Last updated: 2018-06-09Bibliographically approved
Halin Bergström, S., Rudolfsson, S. H. & Bergh, A. (2016). Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype. Neoplasia, 18(3), 152-161
Open this publication in new window or tab >>Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype
2016 (English)In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 18, no 3, p. 152-161Article in journal (Refereed) Published
Abstract [en]

Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen-sensitive, androgen receptor-positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone.

Place, publisher, year, edition, pages
Elsevier, 2016
National Category
Medical Bioscience
Identifiers
urn:nbn:se:umu:diva-119077 (URN)10.1016/j.neo.2016.01.007 (DOI)000372308400003 ()
Available from: 2016-04-15 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
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