scholarly journals The bone microenvironment invigorates metastatic seeds for further dissemination

2020 ◽  
Author(s):  
Weijie Zhang ◽  
Igor L. Bado ◽  
Hai Wang ◽  
Swarnima Singh ◽  
Hin-Ching Lo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Lung Metastases ◽  
Genetic Selection ◽  
Cell Populations ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells ◽  
Promoting Effect ◽  
Primary Tumors ◽  
Clinical Models ◽  
Breast And Prostate Cancer

SUMMARYMetastasis has been considered as the terminal step of tumor progression. However, recent clinical studies suggest that many metastases are seeded from other metastases, rather than primary tumors. Thus, some metastases can further spread, but the corresponding pre-clinical models are lacking. By using several approaches including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. Importantly, dissemination from the bone microenvironment appears to be more aggressive compared to that from mammary tumors and lung metastases. We further uncovered that this metastasis-promoting effect is independent from genetic selection, as single cell-derived cancer cell populations (SCPs) exhibited enhanced metastasis capacity after being extracted from the bone microenvironment. Taken together, our work revealed a previously unappreciated effect of the bone microenvironment on metastasis evolution, and suggested a stable reprogramming process that engenders cancer cells more metastatic.

scholarly journals Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

2021 ◽  
Vol 10 (11) ◽  
pp. 2340
Author(s):  
Lucia Borriello ◽  
John Condeelis ◽  
David Entenberg ◽  
Maja H. Oktay
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metastatic Disease ◽  
Breast Cancer Cells ◽  
Lung Metastases ◽  
Primary Tumors ◽  
Metastatic Burden ◽  
First Time ◽  
Do So

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.

An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nanoclay bone-mimetic scaffolds

MRS Advances ◽  
2019 ◽  
Vol 4 (21) ◽  
pp. 1207-1213 ◽  
Author(s):  
MD Shahjahan Molla ◽  
Dinesh R. Katti ◽  
Kalpana S. Katti
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Cancer Metastasis ◽  
Human Mesenchymal Stem Cells ◽  
Culture Technique ◽  
Complex Nature ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells

ABSTRACTProstate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.

scholarly journals A CTGF‐RUNX2‐RANKL Axis in Breast and Prostate Cancer Cells Promotes Tumor Progression in Bone

2019 ◽  
Vol 35 (1) ◽  
pp. 155-166 ◽  
Author(s):  
Bongjun Kim ◽  
Haemin Kim ◽  
Suhan Jung ◽  
Aree Moon ◽  
Dong‐Young Noh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Breast And Prostate Cancer

Inhibition of 17 -Hydroxysteroid Oxidoreductase by Flavonoids in Breast and Prostate Cancer Cells

1998 ◽  
Vol 217 (3) ◽  
pp. 310-316 ◽  
Author(s):  
S. Makela ◽  
M. Poutanen ◽  
M. L. Kostian ◽  
N. Lehtimaki ◽  
L. Strauss ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Breast And Prostate Cancer

scholarly journals Molecular Decoy to the Y-Box Binding Protein-1 Suppresses the Growth of Breast and Prostate Cancer Cells whilst Sparing Normal Cell Viability

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12661 ◽  
Author(s):  
Jennifer H. Law ◽  
Yvonne Li ◽  
Karen To ◽  
Michelle Wang ◽  
Arezoo Astanehe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Normal Cell ◽  
Binding Protein ◽  
Prostate Cancer Cells ◽  
Breast And Prostate Cancer

Proliferative effect of whey from cows’ milk varying in phyto-oestrogens in human breast and prostate cancer cells

2012 ◽  
Vol 79 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Tina S. Nielsen ◽  
Annika Höjer ◽  
Anne-Maj Gustavsson ◽  
Jens Hansen-Møller ◽  
Stig Purup
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dietary Treatment ◽  
Human Breast ◽  
Prostate Cancer Cells ◽  
Proliferative Effect ◽  
Significant Difference ◽  
Breast And Prostate Cancer ◽  
Mcf 7

Intake of dietary phyto-oestrogens has received a great deal of attention owing to their potential influence on hormone-sensitive cancers such as breast and prostate cancer. Cows’ milk contains phyto-oestrogens and the content varies according to the composition of the feed and the type and amount of legumes used. In this study we evaluated the proliferative effect of milk (whey) with different phyto-oestrogen content in human breast (MCF-7) and prostate cancer cells (PC-3). Milk was obtained from cows fed either a birdsfoot trefoil-timothy silage based ration (B1) or two different red clover silage based diets (R1 and R2) resulting in total phyto-oestrogen contents of 403, 1659 and 1434 ng/ml for the B1, R1 and R2 diets, respectively. Whey was produced from the milk and added to cell culture medium in concentrations up to 10% for MCF-7 cells and 5% for PC-3 cells. Cell proliferation was measured fluorometrically after 7 d for MCF-7 cells and 5 d for PC-3 cells. There was no significant difference in the proliferative effect of whey from the different dietary treatments at any of the whey concentrations tested. An anti-proliferative effect (P<0·01) of 5 and 10% whey was seen when tested in the presence of 10 pmoestradiol in the medium. This effect was independent of dietary treatment of cows. Whey induced a significant (P<0·01) proliferative response in PC-3 cells independent of dietary treatment. Purified equol in concentrations similar to equol concentrations in milk decreased PC-3 cell proliferation, and therefore the stimulatory effect of whey in PC-3 cells is believed to be mediated by other bioactives than equol. In conclusion, our results suggest that using whey in these proliferation assays, it was not possible to discriminate between milk with high or low levels of phyto-oestrogens.

scholarly journals Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene expression by the androgen receptor in prostate cancer cells

2015 ◽  
Vol 26 (11) ◽  
pp. 1971-1984 ◽  
Author(s):  
Julia Lindqvist ◽  
Susumu Y. Imanishi ◽  
Elin Torvaldson ◽  
Marjo Malinen ◽  
Mika Remes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Target Genes ◽  
Growth Promotion ◽  
Intracellular Localization ◽  
Prostate Cancer Cells ◽  
Promoting Effect ◽  
Akt Activation

Contrary to cell cycle–associated cyclin-dependent kinases, CDK5 is best known for its regulation of signaling processes in differentiated cells and its destructive activation in Alzheimer's disease. Recently, CDK5 has been implicated in a number of different cancers, but how it is able to stimulate cancer-related signaling pathways remains enigmatic. Our goal was to study the cancer-promoting mechanisms of CDK5 in prostate cancer. We observed that CDK5 is necessary for proliferation of several prostate cancer cell lines. Correspondingly, there was considerable growth promotion when CDK5 was overexpressed. When examining the reasons for the altered proliferation effects, we observed that CDK5 phosphorylates S308 on the androgen receptor (AR), resulting in its stabilization and differential expression of AR target genes including several growth-priming transcription factors. However, the amplified cell growth was found to be separated from AR signaling, further corroborated by CDK5-depdent proliferation of AR null cells. Instead, we found that the key growth-promoting effect was due to specific CDK5-mediated AKT activation. Down-regulation of CDK5 repressed AKT phosphorylation by altering its intracellular localization, immediately followed by prominent cell cycle inhibition. Taken together, these results suggest that CDK5 acts as a crucial signaling hub in prostate cancer cells by controlling androgen responses through AR, maintaining and accelerating cell proliferation through AKT activation, and releasing cell cycle breaks.

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