Calcium phosphate scaffolds with defined interconnecting channel structure provide a mimetic 3D niche for bone marrow metastasized tumor cell growth

Aveic, Sanja; Davtalab, Roswitha; Vogt, Michael; Weber, Michael H.; Buttler, Patricia; Tonini, Gian Paolo; Fischer, Horst

doi:10.1016/j.actbio.2019.02.030

Cited by 20 publications

(28 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The key problem is to overcome the minimal residual disease and to kill malignant mesenchymal or leukemic cells in the highly vascularized bone and red marrow (RM) areas [ 9 ]. Bone and RM could create a very efficient niche to support the survival and proliferation of the healthy and tumor cells [ 10 ], including metastatic cancer cells [ 11 ]. Aveic et al (2019) concluded that CaP porous material as a simplified three-dimensional (3D) replica of bone and RM niche provides a mimetic 3D niche suitable for invasive tumor cells [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Calcium Phosphate Coating Prepared by Microarc Oxidation Affects hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor-Derived Jurkat T Cells

et al. 2020

View full text Add to dashboard Cite

Calcium phosphate (CaP) materials are among the best bone graft substitutes, but their use in the repair of damaged bone in tumor patients is still unclear. The human Jurkat T lymphoblast leukemia-derived cell line (Jurkat T cells) was exposed in vitro to a titanium (Ti) substrate (10 × 10 × 1 mm3) with a bilateral rough (average roughness index (Ra) = 2–5 μm) CaP coating applied via the microarc oxidation (MAO) technique, and the morphofunctional response of the cells was studied. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscope (EDX) analyses showed voltage-dependent (150–300 V) growth of structural (Ra index, mass, and thickness) and morphological surface and volume elements, a low Ca/PaT ratio (0.3–0.6), and the appearance of crystalline phases of CaHPO4 (monetite) and β-Ca2P2O7 (calcium pyrophosphate). Cell and molecular reactions in 2-day and 14-day cultures differed strongly and correlated with the Ra values. There was significant upregulation of hTERT expression (1.7-fold), IL-17 secretion, the presentation of the activation antigens CD25 (by 2.7%) and CD95 (by 5.15%) on CD4+ cells, and 1.5–2-fold increased cell apoptosis and necrosis after two days of culture. Hyperactivation-dependent death of CD4+ cells triggered by the surface roughness of the CaP coating was proposed. Conversely, a 3.2-fold downregulation in hTERT expression increased the percentages of CD4+ cells and their CD95+ subset (by 15.5% and 22.9%, respectively) and inhibited the secretion of 17 of 27 test cytokines/chemokines without a reduction in Jurkat T cell survival after 14 days of coculture. Thereafter, cell hypoergy and the selection of an hTERT-independent viable CD4+ subset of tumor cells were proposed. The possible role of negative zeta potentials and Ca2+ as effectors of CaP roughness was discussed. The continuous (2–14 days) 1.5–6-fold reductions in the secretion of vascular endothelial growth factor (VEGF) by tumor cells correlated with the Ra values of microarc CaP-coated Ti substrates seems to limit surgical stress-induced metastasis of lymphoid malignancies.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Certainly, CaP-based approaches must contribute main efforts for bone and RM engineering in pathological conditions. However, several publications were devoted to a CaP-based technique to control a behavior of human malignant hematopoietic cells [ 11 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Calcium Phosphate Coating Prepared by Microarc Oxidation Affects hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor-Derived Jurkat T Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Tumors are not homogeneous structures, but rather highly complex tissues involving many cell types, such as tumor, stromal and in ammatory cells [1][2][3]. Cells are primarily supported in solid tumors by the extracellular matrix (ECM), a three-dimensional (3D) dynamic network composed mainly of brous proteins, glycoproteins and proteoglycans [1,4].…”

Section: Introductionmentioning

confidence: 99%

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

López-Carrasco

Martín-Vañó

Burgos‐Panadero

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible.Methods: We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK -mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results: We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions: Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

show abstract

“…Tumors are not homogeneous structures, but rather very complex tissues involving many cell types, such as tumor, stromal and in ammatory cells [1][2][3]. Cells are primarily supported in solid tumors by the extracellular matrix (ECM), a three-dimensional (3D) dynamic network composed mainly of brous proteins, glycoproteins and proteoglycans [1,4].…”

Section: Introductionmentioning

confidence: 99%

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

López-Carrasco¹,

Martín-Vañó²,

Burgos‐Panadero³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We have applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN amplified SK-N-BE(2) and the ALK mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of both cell lines are affected. Results We describe a remarkable subclonal selection of some genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. Specially, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. Genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

show abstract

Calcium phosphate scaffolds with defined interconnecting channel structure provide a mimetic 3D niche for bone marrow metastasized tumor cell growth

Cited by 20 publications

References 43 publications

Calcium Phosphate Coating Prepared by Microarc Oxidation Affects hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor-Derived Jurkat T Cells

Calcium Phosphate Coating Prepared by Microarc Oxidation Affects hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor-Derived Jurkat T Cells

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

Contact Info

Product

Resources

About