Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

Keller, Evan T.

doi:10.1038/aja.2011.50

Cited by 2 publications

(2 citation statements)

References 12 publications

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“…At the same time, tumor cell mobilization from the niche was suggested by an increase in the distance to the nearest bone surface following treatment with AMD3100 compared to control. As osteoblasts are proposed to be a major source of CXCL12 in the bone marrow and serve as docking sites for HSCs and prostate cancer cells, this finding is at least partially supported in our study, which suggests that the spatial distribution of prostate cancer cells in bone marrow correlates with the location of the osteoblastic niche.…”

Section: Discussionsupporting

confidence: 84%

Prostate Cancer Cells Preferentially Home to Osteoblast-rich Areas in the Early Stages of Bone Metastasis: Evidence From In Vivo Models

Wang

Docherty

Brown

et al. 2014

Journal of Bone and Mineral Research

106

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It has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or "niche"). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by twophoton microscopy to be engrafted in the tibiae in close proximity ($40 mm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases.

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Section: Discussionsupporting

confidence: 84%

Prostate Cancer Cells Preferentially Home to Osteoblast-rich Areas in the Early Stages of Bone Metastasis: Evidence From In Vivo Models

Wang

Docherty

Brown

et al. 2014

Journal of Bone and Mineral Research

106

View full text Add to dashboard Cite

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“…Due to late diagnosis and increasing chemoresistance of prostate cancer, the five-year survival rate of patients remains <50% after chemotherapeutic regimens and cytoreductive surgery ( 3 ). Prostate cancer metastasizes and transfers easily, is recurrent and is also resistant to chemotherapy, thus resulting in a high mortality rate ( 4 ). Therefore, development of novel effective and less toxic drugs is urgent for prostate cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells

et al. 2017

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Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism. Scutellarin enhanced the sensitivity of prostate cancer cells to cisplatin. MTT assays revealed that cell viability was significantly decreased in the prostate cancer cells treated with Scutellarin. Flow cytometric analysis indicated that Scutellarin suppressed cell proliferation by promoting G2/M arrest and inducing apoptosis. We employed western blotting to delineate the underlying mechanisms involved in the G2/M arrest and apoptosis. Comet assay and γH2AX immunocytochemistry were used to detect levels of DNA damage in PC3 cells exposed to Scutellarin and/or cisplatin. Our data revealed that Scutellarin significantly induced prostate cancer cell apoptosis by activating the caspase cascade. An increase in the Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential and cell cycle arrest at G2/M phase were accompanied by the apoptosis induction. Additionally, Scutellarin altered the protein expression of cell cycle and apoptosis regulatory genes by downregulating Cdc2, cyclin B1 and Bcl-2 and upregulating caspase-3, caspase-9 and Bax in prostate cancer cells. Furthermore, Scutellarin sensitized PC3 cells to cisplastin treatment in a dose-dependent manner. Taken together, our data confirmed the cytotoxicity of Scutellarin against prostate cancer PC3 cells and provide new findings in regards to Scutellarin sensitizing prostate cancer cells to chemotherapy. Our findings suggest that Scutellarin has potential to be used as a novel antineoplastic therapeutic candidate for prostate cancer patients.

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Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

Cited by 2 publications

References 12 publications

Prostate Cancer Cells Preferentially Home to Osteoblast-rich Areas in the Early Stages of Bone Metastasis: Evidence From In Vivo Models

Prostate Cancer Cells Preferentially Home to Osteoblast-rich Areas in the Early Stages of Bone Metastasis: Evidence From In Vivo Models

Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells

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