3D culture technologies of cancer stem cells: promising ex vivo tumor models

Zhang, Chengye; Yang, Zheng; Dong, Da-Long; Jang, Tae-Su; Knowles, Jonathan C.; Kim, Hae‐Won; Jin, Guang‐Zhen; Xuan, Yanhua

doi:10.1177/2041731420933407

Cited by 55 publications

(51 citation statements)

References 167 publications

(236 reference statements)

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“…In recent years, the growth of breast cancer cells in non-adherent conditions has been increasingly used as a more suitable model for studying aggressive cancer cell growth [ 13 , 14 , 15 ]. In contrast to 2D cultures, the growth of breast cancer cells in non-adherent conditions as three-dimensional (3D) oncospheres leads to enrichment of BCSCs [ 16 , 17 ]. In fact, only these BCSCs are able to grow in non-adherent conditions and express genetic markers of epithelial to mesenchymal transition (EMT) and “stemness”, more similar to their in vivo counterparts [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Role of the NUDT Enzymes in Breast Cancer

Wright

Beato

2021

IJMS

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Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

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Section: Introductionmentioning

confidence: 99%

Role of the NUDT Enzymes in Breast Cancer

Wright

Beato

2021

IJMS

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“…Accordingly, inert biological materials lacking cell attachment could provide a 3D environment. For example, natural polymers such as alginate lack cell adhesion property and could enrich and maintain the stemness properties of CSCs [50,51]. In addition, since it is well known that the stemness maintenance of CSCs is closely associated with the hypoxic environment, the 3D cancer models are expected to replicate the unique characteristics of tumor hypoxic environments, differentiation and niche structure including differentiated cell phenotypes and extracellular matrix [52].…”

Section: Requirement Of Biomaterials In Csc Culturementioning

confidence: 99%

Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro

et al. 2020

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Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion.

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“…In current studies of cancer pathophysiology and drug development, the focus has been laid on 3D in vitro models [ 5 , 6 , 7 ]. 3D culture systems, rather than conventional ones (i.e., monolayers or suspension cultures), allow cells to grow, migrate, interact, and respond to various stimuli analogously to real in vivo behavior [ 8 ]. In vitro studies of CLL are also complicated by the fact that in the conventional cell culture, primary B-CLLs, which are dependent on their natural microenvironment, quickly undergo apoptosis and are not able to establish a stable cell line [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

RGDS-Modified Superporous Poly(2-Hydroxyethyl Methacrylate)-Based Scaffolds as 3D In Vitro Leukemia Model

Svozilová

Plichta

Proks

et al. 2021

IJMS

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Superporous poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate) (P(HEMA-AEMA)) hydrogel scaffolds are designed for in vitro 3D culturing of leukemic B cells. Hydrogel porosity, which influences cell functions and growth, is introduced by adding ammonium oxalate needle-like crystals in the polymerization mixture. To improve cell vitality, cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide is immobilized on the N-(γ-maleimidobutyryloxy)succinimide-activated P(HEMA-AEMA) hydrogels via reaction of SH with maleimide groups. This modification is especially suitable for the survival of primary chronic lymphocytic leukemia cells (B-CLLs) in 3D cell culture. No other tested stimuli (interleukin-4, CD40 ligand, or shaking) can further improve B-CLL survival or metabolic activity. Both unmodified and RGDS-modified P(HEMA-AEMA) scaffolds serve as a long-term (70 days) 3D culture platforms for HS-5 and M2-10B4 bone marrow stromal cell lines and MEC-1 and HG-3 B-CLL cell lines, although the adherent cells retain their physiological morphologies, preferably on RGDS-modified hydrogels. Moreover, the porosity of hydrogels allows direct cell lysis, followed by efficient DNA isolation from the 3D-cultured cells. P(HEMA-AEMA)-RGDS thus serves as a suitable 3D in vitro leukemia model that enables molecular and metabolic assays and allows imaging of cell morphology, interactions, and migration by confocal microscopy. Such applications can prospectively assist in testing of drugs to treat this frequently recurring or refractory cancer.

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3D culture technologies of cancer stem cells: promising ex vivo tumor models

Cited by 55 publications

References 167 publications

Role of the NUDT Enzymes in Breast Cancer

Role of the NUDT Enzymes in Breast Cancer

Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro

RGDS-Modified Superporous Poly(2-Hydroxyethyl Methacrylate)-Based Scaffolds as 3D In Vitro Leukemia Model

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