Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

Holzapfel, Boris Michael; Wagner, Ferdinand; Loessner, Daniela; Holzapfel, Nina Pauline; Thibaudeau, Laure; Crawford, Ross; Ling, Ming-Tat; Clements, Judith A.; Russell, Pamela J.; Hutmacher, Dietmar W.

doi:10.1016/j.biomaterials.2014.01.062

Cited by 93 publications

(107 citation statements)

References 41 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…For example, while bone metastasis is a common clinical presentation of various malignancies such as breast and prostate cancer, the mechanisms involved still remain largely unknown due to the lack of appropriate in vivo models. However, it has been shown that by humanizing the primary tumor site [31,33], or by using human or tissue-engineered bone grafts as target metastatic sites [30,34,35], the osteotropic phenotype can be recapitulated to study the underlying factors involved. The application of such in vivo models is not limited to cancer and has also been used to study various aspects of immunology and toxicology [36,37].…”

Section: Humanized In Vivo Modelsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

155

134

View full text Add to dashboard Cite

The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.

show abstract

Section: Humanized In Vivo Modelsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

155

134

View full text Add to dashboard Cite

show abstract

“…Therefore, to delineate the role of MTA1 in bone metastasis, we utilized the experimental bone metastasis model with injections of cells into the left cardiac ventricle of athymic mice (Chong Seow Khoon, 2015; Holzapfel et al ., 2014; Miftakhova et al ., 2016; Rosol et al ., 2004). Metastases were monitored by weekly bioluminescence imaging until day 34, when mice were sacrificed.…”

Section: Resultsmentioning

confidence: 99%

MTA1 drives malignant progression and bone metastasis in prostate cancer

et al. 2018

View full text Add to dashboard Cite

Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of MTA1 knockdown cells. Mechanistic studies revealed that MTA1 silencing led to a significant decrease in the expression of cathepsin B (CTSB), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E‐cadherin in both cells and xenograft tumors. Moreover, meta‐analysis of clinical samples indicated a positive correlation between MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB‐mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer.

show abstract

“…Our group has already demonstrated that melt electrospun PCL scaffolds are suitable to engineer bone constructs to study species-specific mechanisms in vivo [24,25]. However, the endosteallike ECM deposition by hOBs on melt electrospun PCL scaffolds has not been characterised [47,48].…”

Section: Discussionmentioning

confidence: 99%

“…Melt electrospun written scaffolds made of medical grade poly(ɛ-caprolactone) (PCL) have supported de novo formation of bone in vivo [24,25]. Thus, melt electrospun PCL scaffolds represent a 3D testing platform to tailor characteristic components of the endosteal niche in a highly controlled fashion.…”

Section: Introductionmentioning

confidence: 99%

Endosteal-like extracellular matrix expression on melt electrospun written scaffolds

et al. 2017

Self Cite

View full text Add to dashboard Cite

Endosteal-like extracellular matrix expression on melt electrospun written scaffolds, Acta Biomaterialia (2016), doi: http://dx.doi.org/10. 1016/j.actbio.2016.12.040 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. models that mimic the endosteal microenvironment enable researchers to discover the causes and improve treatments for blood and immune-related diseases. The aim of this study was to establish a physiologically relevant in vitro model using 3D printed scaffolds to assess the contribution of human cells to the formation of a construct that mimics human endosteum. Melt electrospun written scaffolds were used to compare the suitability of primary human osteoblasts (hOBs) and placenta-derived mesenchymal stem cells (plMSCs) in ( when compared to HSCs maintained using tissue culture plastic. This 3D testing platform represents an endosteal bone-like platform and warrants future investigation for the maintenance and expansion of human HSCs.

show abstract

Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

Cited by 93 publications

References 41 publications

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

MTA1 drives malignant progression and bone metastasis in prostate cancer

Endosteal-like extracellular matrix expression on melt electrospun written scaffolds

Contact Info

Product

Resources

About