Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

Micek, Hannah M.; Visetsouk, Mike R; Masters, Kristyn S.; Kreeger, Pamela K.

doi:10.1016/j.isci.2020.101742

Cited by 36 publications

(29 citation statements)

References 104 publications

(121 reference statements)

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“…Increased ECM stiffness is typically linked to tumour aggressiveness [31]. The recognition of the importance of the ECM in regulating developmental and oncogenic processes prompted research on biomaterials that can mimic the properties and dynamics of the ECM and development of scaffold-based 3D models [32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Franchi-Mendes

Eduardo

Domenici

et al. 2021

Cancers

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The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.

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Section: Introductionmentioning

confidence: 99%

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Franchi-Mendes

Eduardo

Domenici

et al. 2021

Cancers

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“…The ECM has been shown to be altered in early tumors, leading to effects on cellular behavior that support cancer progression [36, 37]. Therefore, we sought to characterize the ECM microenvironment of the human fallopian tube and examine how the ECM is altered in early STICs.…”

Section: Discussionmentioning

confidence: 99%

Multi-modal profiling of the extracellular matrix of human fallopian tubes and serous tubal Intraepithelial carcinomas

Renner¹,

Gomez

Visetsouk³

et al. 2021

Preprint

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Recent evidence supports the fimbriae of the fallopian tube as a potential origin site for high-grade serous ovarian cancer (HGSOC). The progression of many solid tumors is accompanied by changes in the microenvironment, including alterations of the extracellular matrix (ECM). The ECM of fallopian tube and HGSOC has not been well characterized. Therefore, we sought to determine the ECM composition of the benign fallopian tube and how it changes with the onset of serous intraepithelial carcinomas (STICs), precursor of HGSOC. The ECM composition of benign human fallopian tube was first defined from a meta-analysis of published proteomic datasets and identified 190 ECM proteins. We then conducted de novo proteomics using ECM enrichment and identified 88 proteins, 7 of which were not identified in prior studies. We further investigated the levels and localization of seven of these ECM proteins (type I, III, and IV collagens, fibronectin, laminin, versican, perlecan) and hyaluronic acid using multi-spectral immunohistochemical staining of fimbriae from patients with benign conditions or STICs. Quantification revealed an increase in stromal fibronectin and a decrease in epithelial versican in STICs. Our results provide an in-depth picture of the ECM in the benign fallopian tube and identified ECM changes that accompany STIC formation.

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“…Indeed, several groups have reported seminal work in studying the individual contributions of matrix properties to cancer progression and metastasis with the use of engineered biomaterials (e.g. synthetic 3D hydrogels; Figure 2B) with tunable physicochemical properties that overcome many of the limitations of natural matrices (Beck et al, 2013;Singh & et al, 2015;Singh et al, 2014;Casey & et al, 2017;Cassereau et al, 2015;Micek et al, 2020). Beck et al (Beck et al, 2013) developed a composite hydrogel to characterize the contributions of matrix stiffness in mammary tumor cell dissemination independent of biochemical signals.…”

Section: Engineered 3d Hydrogels Elucidate the Role Of Ecm Protein Density In Cancer Cell Migrationmentioning

confidence: 99%

“…Furthermore, the continued evolution of 3D hydrogel designs toward biomaterials that can structurally and mechanically recapitulate the tumor ECM and overcome the limitations of biological matrices is paramount to future insights into cancer progression in the context of tumor ECM properties. A recent review by Micek et al (Micek et al, 2020) provides detailed discussion of this approach.…”

Section: Engineered 3d Hydrogels Elucidate the Role Of Ecm Protein Density In Cancer Cell Migrationmentioning

confidence: 99%

Emerging technologies provide insights on cancer extracellular matrix biology and therapeutics

et al. 2021

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Recent engineering technologies have transformed traditional perspectives of cancer to include the important role of the extracellular matrix (ECM) in recapitulating the malignant behaviors of cancer cells. Novel biomaterials and imaging technologies have advanced our understanding of the role of ECM density, structure, mechanics, and remodeling in tumor cell-ECM interactions in cancer biology and have provided new approaches in the development of cancer therapeutics. Here, we review emerging technologies in cancer ECM biology and recent advances in engineered systems for evaluating cancer therapeutics and provide new perspectives on how engineering tools present an opportunity for advancing the modeling and treatment of cancer. This review offers the cell biology and cancer cell biology communities insight into how engineering tools can improve our understanding of cancer ECM biology and therapeutic development.

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Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

Cited by 36 publications

References 104 publications

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Multi-modal profiling of the extracellular matrix of human fallopian tubes and serous tubal Intraepithelial carcinomas

Emerging technologies provide insights on cancer extracellular matrix biology and therapeutics

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