Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

Rijal, Girdhari; Wang, Jing; Yu, Ilhan; Gang, David R.; Chen, Roland; Li, Weimin

doi:10.3390/ijms19102912

Cited by 16 publications

(47 citation statements)

References 33 publications

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“…The recently described system termed "tissue matrix gel" is substantially more complex molecularly beyond its content of collagen. 19 For all three systems, solutions of soluble matrix material were polymerized under standard conditions in regular cell culture medium as detailed in section 2.…”

Section: Resultsmentioning

confidence: 99%

“…[26][27][28][29][30][31][32] TMG contains multiple ECM molecules including fibronectin, laminin, fibrillin, proteoglycan, and so on. 19 Therefore, the enhanced cancer cell migration in TMG may be promoted by one or more of these ECM molecules. Interestingly, there were also striking differences in cell motility between the complex, arguably more physiological 3D matrices, that is, TMG vs the two CDMs.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14][15] 3D matrices used recently that employ physiological extracellular matrix molecules include collagen 3D matrices, cell-derived matrix (CDM), and tissue matrix gel (TMG). [16][17][18][19][20] Collagen 3D matrices based primarily on collagen I are used more frequently. They have the significant advantages of mimicking collagen-rich tissues in vivo, simple molecular composition, and the ability to assemble 3D hydrogels by polymerizing collagen solutions at varying concentrations with the capacity to generate 3D matrix environments that differ in stiffness and matrix pore size for cell migration.…”

Section: Introductionmentioning

confidence: 99%

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Direct comparison of five different 3D extracellular matrix model systems for characterization of cancer cell migration

Shinsato

Doyle

et al. 2020

Cancer Reports

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Background: Three-dimensional (3D) in vitro model systems can bridge the gap between regular two-dimensional cell culture and whole-animal studies. Analyses of cancer cell migration and invasion increasingly use differing 3D systems, which may produce conflicting findings. Aims: We directly compared different 3D extracellular matrix systems for studying cancer cell migration/invasion by analyzing cell morphologies and quantifying aspects of cell migration including speed and directional persistence using automated computer-based cell tracking. Methods and results: We performed direct comparisons of five different 3D extracellular matrix cell culture systems using both HT1080 fibrosarcoma and MDA-MB-231 breast carcinoma cell lines. The reconstituted 3D systems included two types of collagen hydrogel and tissue matrix gel (TMG) vs cell-derived matrices extracted from cultured primary human or cancer-associated fibroblasts. The fibrillar matrix architecture of these systems differed. 3D rat tail collagen and TMG matrices had short, randomly oriented collagen fibrils; bovine collagen had long, larger fibril bundles; and the cellderived matrices were strongly oriented. HT1080 cells displayed rounded morphologies in all three reconstituted 3D matrices but became spindle shaped in the two cell-derived matrices. MDA-MB-231 cell morphologies were elongated in all matrices. Quantitative measures of cell migration parameters differed markedly between the different types of 3D matrix. Comparing the reconstituted matrices, cells migrated the most rapidly and furthest in TMG. Comparing TMG with cell-derived matrices, cells migrated more efficiently in the cell-derived matrices. The most notable differences were in directional persistence of migration, which was greatest in the two cell-derived matrices. Conclusion: The morphologies of matrix fibrils and cell shape, and particularly the efficiency and directionality of cell migration, differed substantially depending on the type of 3D matrix system. We suggest that it is important to employ the 3D model system that most closely resembles the matrix environment being studied for analyses of cancer cell migration and invasion.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct comparison of five different 3D extracellular matrix model systems for characterization of cancer cell migration

Shinsato

Doyle

et al. 2020

Cancer Reports

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“…Three types of native tissue-derived hydrogels, TMG, Col I, and Matrigel, at physiological stiffness were used to study and compare the phenotypes and metabolic profiles of human mammary epithelial cells grown on the matrices. TMG was extracted from porcine breast tissue ECM as we previously reported [40]. Briefly, fresh mammary tissues from female pigs were collected from a local slaughterhouse, homogenized, decellularized, ECM total protein extracted, and reconstituted into hydrogel at desired concentrations for the experiments.…”

Section: Hydrogelmentioning

confidence: 99%

“…To understand breast cancer cell biology at tissuespecific and native environment-mimicry levels, we have recently developed mouse and porcine breast ECM hydrogels, termed tissue matrix gel (TMG), and its derived porous scaffold [39,40]. TMG contains all the proteins found in natural breast ECM, including different types of collagens, laminins, fibronectin, other glycoproteins, and proteoglycans.…”

Section: Introductionmentioning

confidence: 99%

Distinct phenotypes of cancer cells on tissue matrix gel

Ruud

Hiscox

et al. 2020

Breast Cancer Res

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Background: Breast cancer cells invading the connective tissues outside the mammary lobule or duct immerse in a reservoir of extracellular matrix (ECM) that is structurally and biochemically distinct from that of their site of origin. The ECM is a spatial network of matrix proteins, which not only provide physical support but also serve as bioactive ligands to the cells. It becomes evident that the dimensional, mechanical, structural, and biochemical properties of ECM are all essential mediators of many cellular functions. To better understand breast cancer development and cancer cell biology in native tissue environment, various tissue-mimicking culture models such as hydrogel have been developed. Collagen I (Col I) and Matrigel are the most common hydrogels used in cancer research and have opened opportunities for addressing biological questions beyond the two-dimensional (2D) cell cultures. Yet, it remains unclear whether these broadly used hydrogels can recapitulate the environmental properties of tissue ECM, and whether breast cancer cells grown on CoI I or Matrigel display similar phenotypes as they would on their native ECM. Methods: We investigated mammary epithelial cell phenotypes and metabolic profiles on animal breast ECMderived tissue matrix gel (TMG), Col I, and Matrigel. Atomic force microscopy (AFM), fluorescence microscopy, acini formation assay, differentiation experiments, spatial migration/invasion assays, proliferation assay, and nuclear magnetic resonance (NMR) spectroscopy were used to examine biological phenotypes and metabolic changes. Student's t test was applied for statistical analyses. Results: Our data showed that under a similar physiological stiffness, the three types of hydrogels exhibited distinct microstructures. Breast cancer cells grown on TMG displayed quite different morphologies, surface receptor expression, differentiation status, migration and invasion, and metabolic profiles compared to those cultured on Col I and Matrigel. Depleting lactate produced by glycolytic metabolism of cancer cells abolished the cell proliferation promoted by the non-tissue-specific hydrogel. Conclusion: The full ECM protein-based hydrogel system may serve as a biologically relevant model system to study tissue-and disease-specific pathological questions. This work provides insights into tissue matrix regulation of cancer cell biomarker expression and identification of novel therapeutic targets for the treatment of human cancers based on tissue-specific disease modeling.

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Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

et al. 2021

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The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM‐mimetic hydrogels have been widely explored for 3D in vitro disease modeling owing to their bioactive properties that can be further adapted to the biochemical and biophysical properties of native tumors. Gathering on this momentum, herein the current landscape of intrinsically bioactive protein and peptide hydrogels that have been employed for 3D tumor modeling are discussed. Initially, the importance of recreating such microenvironment and the main considerations for generating ECM‐mimetic 3D hydrogel in vitro tumor models are showcased. A comprehensive discussion focusing protein, peptide, or hybrid ECM‐mimetic platforms employed for modeling cancer cells/stroma cross‐talk and for the preclinical evaluation of candidate anticancer therapies is also provided. Further development of tumor‐tunable, proteinaceous or peptide 3D microtesting platforms with microenvironment‐specific biophysical and biomolecular cues will contribute to better mimic the in vivo scenario, and improve the predictability of preclinical screening of generalized or personalized therapeutics.

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Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

Cited by 16 publications

References 33 publications

Direct comparison of five different 3D extracellular matrix model systems for characterization of cancer cell migration

Direct comparison of five different 3D extracellular matrix model systems for characterization of cancer cell migration

Distinct phenotypes of cancer cells on tissue matrix gel

Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

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