Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

Moccia, Carmen; Haase, Kristina

doi:10.3389/fbioe.2021.694218

Cited by 24 publications

(22 citation statements)

References 171 publications

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“…Modelling the complexity of tumour progression, especially the steps of metastasis formation, also requires microfluidics and several host tissues to be combined in novel in vitro test systems [82][83][84][85][86][87][88][89][90][91][92][93]. The continuously emerging data about such devices for BC and more complex BC models were summarised by Moccia and Haase [94,95]. Furthermore, we have to take into account that these bioengineered models and their increasing complexity are correlated inversely with adequate standardizations and validations, further elevating the costs.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

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Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.

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Section: Discussionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

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“…CAF-S2 is characteristic for luminal-like tumors [48]. The significant presence of CAF-S2 is also seen in normal breast tissue, suggesting that CAFs in luminal BC may be derived from normal resident fibroblasts [47,48]. In aggressive BC subtypes, CAF-S1 and CAF-S4 are characteristic: HER2+ tumors are enriched in CAF-S4, while TNBC tumors have a high presence of CAF-S4 and CAF-S1 [48].…”

Section: Other Tme Componentsmentioning

confidence: 99%

“…Fibroblasts are stromal cells involved in supporting tissues by secreting proteins and remodeling the extracellular matrix (ECM). Breast TME contains carcinoma-associated fibroblasts (CAFs), which contribute to tumor progression by secreting tumor-promoting factors (e.g., chemokines and matrix metalloproteinases) [45][46][47]. Specific CAF subsets were detected in different BC subtypes.…”

Section: Other Tme Componentsmentioning

confidence: 99%

“…Additionally, breast TME contains cancer-associated adipocytes (CAAs), which express proteases that degrade the ECM. CAAs are characterized by reduced lipid content, expression of specific adipokines and proteases, and increased pro-inflammatory cytokine production [47]. Fragmentation of ECM by metalloproteinases and remodeling enzymes can promote the penetration of CAFs [50].…”

Section: Other Tme Componentsmentioning

confidence: 99%

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Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

Čelešnik

Potočnik

2022

Cancers

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Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.

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“…For example, autologous peripheral blood monocytes derived from patient blood samples have been successfully added into the corresponding colon and lung cancer organoid setup (Dijkstra et al, 2018). Tumor-ona-chip technology may also enable a better understanding of the role of the immune system and its incorporation into an organoid model setup (Moccia and Haase, 2021).…”

Section: Introductionmentioning

confidence: 99%

A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy

Carter

Hartkopf

Wagner

et al. 2022

Front. Mol. Biosci.

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Background: Although several oncolytic viruses have already been tested in early-stage clinical studies of breast cancer, there is still an urgent need to develop patient-derived experimental systems that mimic the response of breast cancer to oncolytic agents in preparation of testing different oncolytic viruses in clinical trials. We addressed this need by developing a protocol to study the effects of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue.Methods: We used an established three-dimensional organoid model derived from tissue of 10 patients with primary breast cancer. We developed an experimental protocol for infecting organoid cultures with oncolytic viruses and compared the oncolytic effects of a measles vaccine virus (MeV) and a vaccinia virus (GLV) genetically engineered to express either green fluorescent protein (MeV-GFP) and red fluorescent protein (GLV-0b347), respectively, or a suicide gene encoding a fusion of cytosine deaminase with uracil phosphoribosyltransferase (MeV-SCD and GLV-1h94, respectively), thereby enabling enzymatic conversion of the prodrug 5-fluorocytosine (5-FC) into cytotoxic compounds 5-fluorouracil (5-FU) and 5-fluorouridine monophosphate (5-FUMP).Results: The method demonstrated that all oncolytic viruses significantly inhibited cell viability in organoid cultures derived from breast cancer tissue. The oncolytic effects of the oncolytic viruses expressing suicide genes (MeV-SCD and GLV-1h94) were further enhanced by virus-triggered conversion of the prodrug 5-FC to toxic 5-FU and toxic 5-FUMP.Conclusions: We were able to develop a protocol to assess the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene (MeV-SCD and GLV-1h94) in the presence of the prodrug 5-FC. The model therefore provides a promising in vitro method to help further testing and engineering of new generations of virotherapeutic vectors for in vivo use.

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Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

Cited by 24 publications

References 171 publications

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy

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