Changes in the transcriptome profile of breast cancer cells grown as spheroids

Muñoz-Galindo, Laura; Meléndez-Zajgla, Jorge; Pacheco-Fernández, Thalia; Rodrı́guez-Sosa, Miriam; Mandujano-Tinoco, Edna Ayerim; Vázquez-Santillán, Karla; Castro-Oropeza, Rosario; Lizárraga, Floria; Sanchez-Lopez, José Manuel; Maldonado, Vilma

doi:10.1016/j.bbrc.2019.06.155

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…However, these small spheroids tend not to be physiologically relevant, as they do not fully represent the sizes of even the smallest clinically relevant avascular tumors found in patients, which normally exceed a size threshold of 400 µm [23][24][25]. This size differential is important because spheroids larger than 400-500 µm exhibit tumor-like oxygen gradients and hypoxic conditions in their cores [21,26], while hypoxia has been described as a contributor to the resistance to anti-cancer drugs exhibited by real tumors [21,27,28]. In general, novel strategies that are assisted by bioprinting [29] or microfluidicsbased methods [22,30,31] provide better control of the critical parameters of spheroids (i.e.…”

Section: Introductionmentioning

confidence: 99%

Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs)

Gallegos-Martínez¹,

Lara-Mayorga²,

Samandari³

et al. 2022

Biofabrication

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Cancer continues to be a leading cause of mortality in modern societies; therefore, improved and more reliable in vitro cancer models are needed to expedite fundamental research and anti-cancer drug development. Here, we describe the use of a miniaturized continuous stirred tank reactor (mCSTR) to first fabricate and mature cancer spheroids (i.e, derived from MCF7 cells, DU145 cells, and a mix of MCF7 cells and fibroblasts), and then to conduct anti-cancer drug assays under continuous perfusion. This 3 mL mCSTR features an off-center agitation system that enables homogeneous chaotic laminar mixing at low speeds to support cell aggregation. We incubated cell suspensions for 3 days in ultra-low-adherence (ULA) plates to allow formation of discoid cell aggregates (~600 µm in diameter). These cell aggregates were then transferred into mCSTRs and continuously fed with culture medium. We characterized the spheroid morphology and the expression of relevant tumor biomarkers at different maturation times for up to 4 weeks. The spheroids progressively increased in size during the first 5 to 6 days of culture to reach a steady diameter between 600 and 800 µm. In proof-of-principle experiments, we demonstrated the use of this mCSTR in anti-cancer drug testing. Three drugs commonly used in breast cancer treatment (doxorubicin, docetaxel, and paclitaxel) were probed at different concentrations in MCF7 derived spheroids. In these experiments, we evaluated cell viability, glucose consumption, spheroid morphology, lactate dehydrogenase activity, and the expression of genes associated with drug resistance (ABCB1 and ABCC1) and anti-apoptosis (Bcl2). We envision the use of this agitated system as a tumor-on-a-chip platform to expedite efficacy and safety testing of novel anti-cancer drugs and possibly in personalized medicine applications.

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Section: Introductionmentioning

confidence: 99%

Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs)

Gallegos-Martínez¹,

Lara-Mayorga²,

Samandari³

et al. 2022

Biofabrication

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“…In addition, Mingming’s findings suggest that that vimentin levels regulate LINC00052 in BC. In accordance, Pacheco-Marin and Muñoz-Galindo also reported decreased levels of LINC00052 in three-dimensional breast cancer multicellular spheroids, which mimics the biology of avascular tumours in vivo , as the cells become more aggressive [ 16 , 17 ]. Similarly, our research group showed that LINC00052 is associated with improved overall survival in breast cancer patients and that LINC00052 inhibits BC cell migration through modulation of the cytoskeleton and NOTCH/β–catenin/NFkB signalling pathways [ 20 ].…”

Section: Introductionmentioning

confidence: 73%

Decoding LINC00052 role in breast cancer by bioinformatic and experimental analyses

Sanchez-Lopez,

Juarez-Mancera,

Bustamante

et al. 2024

RNA Biology

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“…In a study employing tumor spheroids derived from breast cancer, culturing cells in a 3D environment, led to a significant alteration in the transcriptome of breast cancer cells with one of the major changes being deregulated cholesterol homeostasis ( 93 ). These findings are supported by a study conducted by Ehmsen et al.…”

Section: The Utility Of 3d Models In Studying Molecular Mechanisms Of...mentioning

confidence: 99%

The utility of 3D models to study cholesterol in cancer: Insights and future perspectives

2023

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Cholesterol remains a vital molecule required for life; however, increasing evidence exists implicating cholesterol in cancer development and progression. Numerous studies investigating the relationship between cholesterol and cancer in 2-dimensional (2D) culture settings exist, however these models display inherent limitations highlighting the incipient need to develop better models to study disease pathogenesis. Due to the multifaceted role cholesterol plays in the cell, researchers have begun utilizing 3-dimensional (3D) culture systems, namely, spheroids and organoids to recapitulate cellular architecture and function. This review aims to describe current studies exploring the relationship between cancer and cholesterol in a variety of cancer types using 3D culture systems. We briefly discuss cholesterol dyshomeostasis in cancer and introduce 3D in-vitro culture systems. Following this, we discuss studies performed in cancerous spheroid and organoid models that focused on cholesterol, highlighting the dynamic role cholesterol plays in various cancer types. Finally, we attempt to provide potential gaps in research that should be explored in this rapidly evolving field of study.

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Changes in the transcriptome profile of breast cancer cells grown as spheroids

Cited by 8 publications

References 31 publications

Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs)

Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs)

Decoding LINC00052 role in breast cancer by bioinformatic and experimental analyses

The utility of 3D models to study cholesterol in cancer: Insights and future perspectives

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