CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

Mi, Kun; Xing, Zhihua

doi:10.2147/ijn.s66723

Cited by 27 publications

(13 citation statements)

References 40 publications

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“…3e,f ) showed peripheral nuclear alignment and apical-basal polarity maintained by the precise arrangement of actin filaments ( Fig. 3e ) 30 , namely at interior luminal surface and at cell-cell junctions, and stained positively for functional E-cadherin ( Fig. 3f ), a prototypical epithelial marker, which was localized at the cell membrane, stabilizing cell-cell contacts within spheroids.…”

Section: Resultsmentioning

confidence: 99%

A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion

Bidarra

Oliveira

Rocha

et al. 2016

Sci Rep

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Epithelial-to-mesenchymal transitions (EMT) are strongly implicated in cancer dissemination. Intermediate states, arising from inter-conversion between epithelial (E) and mesenchymal (M) states, are characterized by phenotypic heterogeneity combining E and M features and increased plasticity. Hybrid EMT states are highly relevant in metastatic contexts, but have been largely neglected, partially due to the lack of physiologically-relevant 3D platforms to study them. Here we propose a new in vitro model, combining mammary E cells with a bioengineered 3D matrix, to explore phenotypic and functional properties of cells in transition between E and M states. Optimized alginate-based 3D matrices provided adequate 3D microenvironments, where normal epithelial morphogenesis was recapitulated, with formation of acini-like structures, similar to those found in native mammary tissue. TGFβ1-driven EMT in 3D could be successfully promoted, generating M-like cells. TGFβ1 removal resulted in phenotypic switching to an intermediate state (RE cells), a hybrid cell population expressing both E and M markers at gene/protein levels. RE cells exhibited increased proliferative/clonogenic activity, as compared to M cells, being able to form large colonies containing cells with front-back polarity, suggesting a more aggressive phenotype. Our 3D model provides a powerful tool to investigate the role of the microenvironment on metastable EMT stages.

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Section: Resultsmentioning

confidence: 99%

A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion

Bidarra

Oliveira

Rocha

et al. 2016

Sci Rep

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show abstract

“…The increased number of dormant cells combined with the phenotype of enhanced expression of P‐gp gene/protein provides a clue to the enrichment of BCSCs in the 3D cultures. BCSCs are described as a subpopulation of breast cancer cells that share several features of normal stem cells, such as self‐renewal, pluripotency, and altered gene expression (Beça et al, ; Mi & Xing, ). Identification of BCSCs from breast cancer cells has been based mainly on CD 24− /CD 44+ or aldehyde dehydrogenase markers (Ponti et al, ; Velasco‐Velázquez, Homsi, De La Fuente, & Pestell, ).…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional tissue culture model of human breast cancer for the evaluation of multidrug resistance

Ding

Liu

et al. 2018

J Tissue Eng Regen Med

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Multidrug resistance (MDR) is one of the major obstacles to improving outcomes of chemotherapy in tumour patients. However, progress has been slow to overcome this phenomenon due to the limitations of current cell/tissue models in recapitulating MDR behaviour of tumour cells in vitro. To address this issue, a more pathologically relevant, three-dimensional (3D) culture of human breast cancer cells was developed by seeding the adriamycin-resistant cells MCF-7R in silk-collagen scaffolds. The cultures of the parental cell line MCF-7 served as controls. Distinct growth profiles of MCF-7R and MCF-7 cells were observed when they were cultured in the scaffolds in comparison with those in the monolayer culture, including cell proliferation, cellular aggregate formation, and expression of drug resistance-related genes/proteins. Moreover, the 3D cultures of these cell lines especially the cultures of MCF-7R exhibited a significantly enhanced drug resistance evidenced by their increased IC values to the anticancer drugs and improved drug efflux capability. An altered cell cycle distribution and improved percentage of breast cancer stem cell (BCSC)-like cells was also found in the present study. This might play an important role in promoting the drug-resistance production in those 3D cultures. Thus, we established improved 3D cultures of MDR human breast cancer. It would provide a robust tissue model for use to evaluate the efficacy of anticancer drugs, explore mechanisms of MDR, and enrich BCSCs in vitro.

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“…Collagen-based scaffolds supported directional metastasis of BC cells with invasive phenotypes compared to Matrigel or RADA16 peptide scaffolds, which could be enhanced by the increased collagen density. 83 – 85 A bovine serum albumin (BSA) scaffold with fibronectin (FN) showed desirable BC cell adhesion and migration compared with the BSA scaffold alone. 86 …”

Section: Three-dimensional Approaches To Model Cancer Bone Metastasismentioning

confidence: 99%

Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis

Qiao

Tang

2018

Bone Res

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Cancer metastasis to bone is a three-dimensional (3D), multistep, dynamic process that requires the sequential involvement of three microenvironments, namely, the primary tumour microenvironment, the circulation microenvironment and the bone microenvironment. Engineered 3D approaches allow for a vivid recapitulation of in vivo cancerous microenvironments in vitro, in which the biological behaviours of cancer cells can be assessed under different metastatic conditions. Therefore, modelling bone metastasis microenvironments with 3D cultures is imperative for advancing cancer research and anti-cancer treatment strategies. In this review, multicellular tumour spheroids and bioreactors, tissue engineering constructs and scaffolds, microfluidic systems and 3D bioprinting technology are discussed to explore the progression of the 3D engineering approaches used to model the three microenvironments of bone metastasis. We aim to provide new insights into cancer biology and advance the translation of new therapies for bone metastasis.

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CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

Cited by 27 publications

References 40 publications

A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion

A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion

Three-dimensional tissue culture model of human breast cancer for the evaluation of multidrug resistance

Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis

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