Rapid fabrication of collagen bundles mimicking tumor-associated collagen architectures

Gong, Xiangyu; Kulwatno, Jonathan; Mills, Kristen

doi:10.1016/j.actbio.2020.03.019

Cited by 33 publications

(18 citation statements)

References 61 publications

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“…39 , 40 At the same time, the aligned collagen bundles, which mimic the structure of tumor-related collagen fibers, have been shown to trigger cancer cell contact guidance and enhance directional migration. 41 , 42 Bio-interface anisotropy regulated the cell’s morphology and mediated the migration pattern. Morphologically, the cells on anisotropic nanofibers showed an elongated spindle shape.…”

Section: Discussionmentioning

confidence: 99%

Templated Three-Dimensional Engineered Bone Matrix as a Model for Breast Cancer Osteolytic Bone Metastasis Process

Sun¹,

Huang²,

Luo³

et al. 2021

IJN

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Purpose Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis. Methods In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix. Results A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis. Conclusion An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Templated Three-Dimensional Engineered Bone Matrix as a Model for Breast Cancer Osteolytic Bone Metastasis Process

Sun¹,

Huang²,

Luo³

et al. 2021

IJN

View full text Add to dashboard Cite

show abstract

“…Many techniques allow alteration of fiber size independently of overall collagen concentration or bulk Young's modulus (Carey et al, 2012;Oh et al, 2020;Seo et al, 2020), although these approaches have been limited by issues such as poor control over fiber size modulation, non-physiological fiber sizes, or use of specialized equipment. There has been recent progress on this front, wherein simple modifications to the common collagen gelation protocol yielded physiological fiber sizes (Gong et al, 2020), although there remains a need for accessible technologies capable of modulating fiber features in a controlled manner. Another limitation that remains across these fiber-focused studies is that they are typically conducted with collagen-only materials and have not included other ECM cues prevalent in the tumor environment (e.g., fibronectin, laminin, HA).…”

Section: Future Directionsmentioning

confidence: 99%

Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

et al. 2020

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Clinical evidence supports a role for the extracellular matrix (ECM) in cancer risk and prognosis across multiple tumor types, and numerous studies have demonstrated that individual ECM components impact key hallmarks of tumor progression (e.g., proliferation, migration, angiogenesis). However, the ECM is a complex network of fibrillar proteins, glycoproteins, and proteoglycans that undergoes dramatic changes in composition and organization during tumor development. In this review, we will highlight how engineering approaches can be used to examine the impact of changes in tissue architecture, ECM composition (i.e., identity and levels of individual ECM components), and cellular-and tissue-level mechanics on tumor progression. In addition, we will discuss recently developed methods to model the ECM that have not yet been applied to the study of cancer.

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“…In general, changes in the ECM organization will also change the cells within the tissue including their interactions with the ECM and other cells [66]. Recently, methods to directly test how collagen and its organization affect cell properties have been developed, including electrospun fibers made to mimic the tumor microenvironment, which promoted normal epithelial cells to adapt a mesenchymal morphology [72] and in vitro gels that mimic tumor-associated collagen architectures with large, aligned collagen bundles, which elicited cancer cell contact guidance and enhanced their directional migration [73]. While the collagen organization in FMT likely affects the neoplastic and cancer associated fibroblasts within the tumor, immune cells may also alter their behavior based on tumor ECM and collagen organization.…”

Section: Plos Onementioning

confidence: 99%

Intratumoral collagen signatures predict clinical outcomes in feline mammary carcinoma

et al. 2020

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Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.

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Rapid fabrication of collagen bundles mimicking tumor-associated collagen architectures

Cited by 33 publications

References 61 publications

Templated Three-Dimensional Engineered Bone Matrix as a Model for Breast Cancer Osteolytic Bone Metastasis Process

Templated Three-Dimensional Engineered Bone Matrix as a Model for Breast Cancer Osteolytic Bone Metastasis Process

Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

Intratumoral collagen signatures predict clinical outcomes in feline mammary carcinoma

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