The biomimetic extracellular matrix: a therapeutic tool for breast cancer research

Tamayo-Angorrilla, Marta; Andrés, Julia López de; Jiménez, Gema; Marchal, Juan A.

doi:10.1016/j.trsl.2021.11.008

Cited by 16 publications

(27 citation statements)

References 161 publications

(181 reference statements)

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“…Tumor-derived dECM has previously been used as a substrate for in vitro cell culture studies and cancer modeling. In some reports, it has been processed as hydrogels and further as inks for the printing and development of 3D bioengineered structures ( 34 , 59 ). In other reports, tumor-derived dECM has been used as a 3D scaffold for cell-seeding purposes ( 48 , 49 , 60 – 63 ).…”

Section: Discussionmentioning

confidence: 99%

“…Matrices from normal tissue can be used to recognize novel genes inducing cancer or the interactions between cancer cells and healthy ECM. On the other hand, decellularized tumor tissue is more appropriate for studying the influence of pathological ECM on controlling cancer cell function at primary or metastatic sites and the role of ECM as a modulator of cell behavior ( 34 – 37 ).…”

Section: Introductionmentioning

confidence: 99%

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Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

et al. 2022

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In vitro cell culture studies are common in the cancer research field, and reliable biomimetic 3D models are needed to ensure physiological relevance. In this manuscript, we hypothesized that decellularized xenograft tumors can serve as an optimal 3D substrate to generate a top-down approach for in vitro tumor modeling. Multiple tumor cell lines were xenografted and the formed solid tumors were recovered for their decellularization by several techniques and further characterization by histology and proteomics techniques. Selected decellularized tumor xenograft samples were seeded with the HCC1806 human triple-negative breast cancer (TNBC) basal-like subtype cell line, and cell behavior was compared among them and with other control 2D and 3D cell culture methods. A soft treatment using Freeze-EDTA-DNAse allows proper decellularization of xenografted tumor samples. Interestingly, proteomic data show that samples decellularized from TNBC basal-like subtype xenograft models had different extracellular matrix (ECM) compositions compared to the rest of the xenograft tumors tested. The in vitro recellularization of decellularized ECM (dECM) yields tumor-type–specific cell behavior in the TNBC context. Data show that dECM derived from xenograft tumors is a feasible substrate for reseeding purposes, thereby promoting tumor-type–specific cell behavior. These data serve as a proof-of-concept for further potential generation of patient-specific in vitro research models.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

et al. 2022

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“…Biomimetic models such as the decellularized ECM recapitulates the complex ECM microenvironment of the mammary glands and can be useful tools to allow a better understanding of cell-ECM interactions. Although these approaches to treating breast cancer are still new, it may shed light on the tumorigenesis of the mammary gland cancer and open new treatment paradigms ( Wishart et al, 2020 ; Tamayo-Angorrilla et al, 2021 ).…”

Section: Implication Of Adhesion Molecules In Diseasesmentioning

confidence: 99%

Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche

Lim

Banerjee²,

Biswas³

et al. 2022

Front. Cell Dev. Biol.

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Stem cells have been shown to play an important role in regenerative medicine due to their proliferative and differentiation potential. The challenge, however, lies in regulating and controlling their potential for this purpose. Stem cells are regulated by growth factors as well as an array of biochemical and mechanical signals. While the role of biochemical signals and growth factors in regulating stem cell homeostasis is well explored, the role of mechanical signals has only just started to be investigated. Stem cells interact with their niche or to other stem cells via adhesion molecules that eventually transduce mechanical cues to maintain their homeostatic function. Here, we present a comprehensive review on our current understanding of the influence of the forces perceived by cell adhesion molecules on the regulation of stem cells. Additionally, we provide insights on how this deeper understanding of mechanobiology of stem cells has translated toward therapeutics.

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“…In the last 15 years, three-dimensional (3D) organoid technologies have been proposed as innovative tools for therapeutic screening and precision medicine in cancer treatment [ 8 , 9 ]. Addressing the high genomic instability and altered phenotypes of 2D cultures, 3D organoid culture systems from patient specimens better retain the characteristics of a patient’s original tumor [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…An added advantage of PEG derivatives is its use in bioprinting [ 31 ], which may open the door to automated and medium-to-high-throughput manufacturing of BCa PDO models [ 32 ]. Yet, the limited bioactive sites and lack of protein absorption of PEG has prompted the field to explore semi-synthetic polymers [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids

et al. 2023

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3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

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The biomimetic extracellular matrix: a therapeutic tool for breast cancer research

Cited by 16 publications

References 161 publications

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche

GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids

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