Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

Shiozawa, Yusuke; McGee, Samantha; Pienta, Michael J.; McGregor, Natalie; Jung, Younghun; Yumoto, Kenji; Wang, Jingcheng; Berry, Janice E.; Pienta, Kenneth J.; Taichman, Russell S.

doi:10.1002/jcb.24592

Cited by 12 publications

(8 citation statements)

References 39 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar studies with prostate cancer cell lines showed that GAS6 induces prostate cancer DTC dormancy but only when AXL receptor signalling predominates. This evidence supports the idea that HSC niche signals could induce dormancy 68–70,74 .…”

Section: Microenvironmental Regulation Of Dormancysupporting

confidence: 87%

Mechanisms of disseminated cancer cell dormancy: an awakening field

2014

View full text Add to dashboard Cite

Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we attempt to integrate this information and highlight both the weaknesses and the strengths in the field to provide a framework to understand and target this crucial step in cancer progression.

show abstract

Section: Microenvironmental Regulation Of Dormancysupporting

confidence: 87%

Mechanisms of disseminated cancer cell dormancy: an awakening field

2014

View full text Add to dashboard Cite

show abstract

“…Furthermore, RANKLmediated signalling from prostate cancer cells is shown to establish the pre-metastatic niche and induce colonisation and metastasis to bone (Chu et al 2014). In addition, bone resorption disrupts adhesion of HSCs to niche components that maintain cell quiescence resulting in proliferation (Shiozawa et al 2013). It is therefore likely that other mechanisms that disrupt the endosteal niche, including castration-induced bone loss, may have similar effects altering integrin interactions that maintain tumour cells in a quiescent state (Barkan et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Castration-induced bone loss triggers growth of disseminated prostate cancer cells in bone

Ottewell¹,

Wang²,

Meek³

et al. 2014

Endocrine Related Cancer

View full text Add to dashboard Cite

Up to 90% of patients with castrate-resistant prostate cancer develop bone metastases, and the majority of these men have received androgen deprivation therapy known to cause bone loss. Whether this treatment-induced change to the bone microenvironment affects disseminated tumour cells, potentially stimulating development of bone metastasis, remains to be determined. The objective of this study was to use an in vivo model mimicking androgen ablation to establish the effects of this intervention on disseminated prostate cancer cells in bone. We mimicked the effects of androgen deprivation on bone metastasis by castrating 12-week-old BALB/c nude mice that had disseminated, hormone-insensitive PC3 prostate cancer cells present in the long bones. Castration caused increased bone resorption and loss of bone volume, compared with sham operation. In addition, castration triggered growth of disseminated PC3 cells to form bone metastasis in 70% of animals. In contrast, only 10% of sham-operated animals had detectable long bone tumours. Weekly administration of 100 μg/kg zoledronic acid (ZOL) prevented castration-induced tumour growth in bone and increased bone volume, but did not eliminate the disseminated tumour cells. ZOL had no effect on tumour growth in the sham-operated animals, despite causing a significant increase in bone volume. This is the first demonstration that, in a model of prostate cancer bone metastasis, mimicking androgen ablation results in growth of disseminated tumour cells in bone through osteoclast-mediated mechanisms. We provide the first biological evidence supporting the administration of ZOL to prostate cancer patients at the time of androgen ablation to prevent subsequent relapse in bone.

show abstract

“…Some studies provide evidence that Epo/Epo-R axis activation leads to tumor cell proliferation; while other studies demonstrate Epo/Epo-R activation did not support tumor cell growth specifically [29] . Interestingly, Shiozawa et al [30] demonstrated that Epo did not stimulate PCa tumor cell (using PCa cell lines) proliferation in vitro , or enhance metastasis in vivo ; however, these authors did demonstrate an increased tumor cell resistance to apoptosis resulting in PCa cell survival. Similarly, Todaro et al [31] reported that Epo stimulation increased resistance of breast cancer stem-like cells (BCSC) isolated from patient tumors to chemotherapeutics, doxorubicin and 5-FU, in vitro and in a subcutaneous mouse model.…”

Section: Erythropoietin and The Hsc Nichementioning

confidence: 98%

The role of hematopoietic stem cell niche in prostate cancer bone metastasis

Decker

Jung

Cackowski

et al. 2016

Journal of Bone Oncology

View full text Add to dashboard Cite

Approximately 80% of prostate cancers exhibit some degree of bone metastasis. The role of the bone marrow and the hematopoietic stem cell (HSC) niche in attracting metastatic cells and maintaining dormancy of disseminated tumor cells (DTCs) is an increasingly important topic towards the development of novel prostate cancer therapies. This paper reviews aspects of the HSC niche that lead to prostate cancer cell homing and dormancy in the bone marrow. This review also discusses the role of DTCs in the niche environment and discusses the role of erythropoietin in targeting DTCs within the HSC niche.

show abstract

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

Cited by 12 publications

References 39 publications

Mechanisms of disseminated cancer cell dormancy: an awakening field

Mechanisms of disseminated cancer cell dormancy: an awakening field

Castration-induced bone loss triggers growth of disseminated prostate cancer cells in bone

The role of hematopoietic stem cell niche in prostate cancer bone metastasis

Contact Info

Product

Resources

About