Androgen‐insensitive prostate cancer cells transiently respond to castration treatment when growing in an androgen‐dependent prostate environment

Halin, Sofia; Hammarsten, Peter; Wikström, Pernilla; Bergh, Anders

doi:10.1002/pros.20473

Cited by 57 publications

(85 citation statements)

References 25 publications

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“…After orthotopic inoculation in nude mice, PC-3 cells also produced smaller primary and pelvic lymph node (PLN) metastatic tumors when combined with WPMY1-ARsi than with WPMY1-v cells (Niu et al, 2008b). Similar in vivo androgen/AR-dependent tumor growth were also observed using other AR-negative prostate cancer cell lines (Marques et al, 2005;Halin et al, 2007), and LNCaP cells might grow more aggressively on orthotopic transplantation after being co-inoculated with rat urogenital mesenchyme or bone marrow fibroblasts (Gleave et al, 1991). Together, these in vitro and in vivo findings suggested that the stromal AR might function as a proliferation stimulator to promote prostate tumor progression and metastasis.…”

Section: Ar Dual Functions In Prostate Cancer Progression and Metastasismentioning

confidence: 62%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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Prostate cancer is one of the major causes of cancerrelated death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormonerefractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/ AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR overexpression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells.

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Section: Ar Dual Functions In Prostate Cancer Progression and Metastasismentioning

confidence: 62%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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“…In line with this, implantation of tumor cells into the rat prostate resulted in adaptive changes in the surrounding ipsilateral but also in the contralateral prostate lobe. 19,20 Adaptions in the surrounding stroma, in part mediated by macrophages recruited to the tissue around tumors, 20 such as growth of the supporting vasculature and tissue remodulation are probably necessary for subsequent tumor growth and metastasis. 19 -21 Such responses in tumor-adjacent nonmalignant tissues are morphologically similar to those seen around wounds, 8,51 and the gene expression in the normal rat prostate tissue surrounding an implanted AT-1 prostate cancer is similar to that in wounding and inflammation (Adamo et al, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…Tumor size was determined by measuring the volume density of tumor in the ventral prostate using a stereologic approach and then multiplying the volume density by the ventral prostate lobe weight as previously described. 19 All animal work was approved by the local ethical committee for animal research.…”

Section: Animal Experimentsmentioning

confidence: 99%

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Josefsson

Adamo

Hammarsten

et al. 2011

The American Journal of Pathology

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Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome. (Am J Pathol

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“…18 Another group was treated as above and castrated at day 7 and examined at day 14. Two additional groups were injected with phosphatebuffered saline (PBS) or pretreated with the inhibitor of mast cell degranulation, Sodium Cromoglycate (SDG, Sanofi-Aventis AB, Stockholm, Sweden) at a dose of 100 mg/kg/day intraperitoneal (i.p.)…”

Section: Ortothopic Implantation Of At-1 Tumor Cells and Treatment Wimentioning

confidence: 99%

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Johansson

Rudolfsson

Hammarsten

et al. 2010

The American Journal of Pathology

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189

187

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Mast cells affect growth in various humanCancer growth is dependent on the reciprocal interaction between tumor cells and their microenvironment. Cancerassociated fibroblasts, 1 vascular cells, and inflammatory cells such as macrophages [2][3][4] have been shown to promote prostate tumor growth. Mast cells are also of importance for tumor growth and have been shown to affect angiogenesis 5-7 but are also potent regulators of inflammation and thus their specific function during tumor progression is complex and shows significant plasticity. 8 -10 Their role in prostate cancer (PC) in patients was recently explored in two separate studies using tryptase and c-Kit as markers for mast cells. These studies lacked the discrepancy between intra-and peritumoral mast cells and did not identify mast cells as independent prognostic variables. One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. 13Castration therapy is the gold standard for treatment of patients with metastatic PC, but in the majority of cases the formation of castrate-resistant prostate tumors is inevitable. The mechanisms behind the relapse are not fully understood but could be related to changes in the androgen receptor and the tumor stroma.

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Androgen‐insensitive prostate cancer cells transiently respond to castration treatment when growing in an androgen‐dependent prostate environment

Abstract: Androgen-independent tumor cell respond to castration when growing in an androgen-dependent environment. The presence of a tumor influences the castration response in the surrounding normal tissue. The microenvironment determines how prostate epithelial cells respond to castration.

Cited by 57 publications

References 25 publications

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

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