Engineering Breast Cancer Microenvironments and 3D Bioprinting

Belgodere, Jorge A.; King, Connor T.; Bursavich, Jacob; Burow, Matthew E.; Martin, Elizabeth C.; Jung, Jangwook P.

doi:10.3389/fbioe.2018.00066

Cited by 90 publications

(70 citation statements)

References 221 publications

(280 reference statements)

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“…In particular, the TME contributes to tumor heterogeneity, strongly affecting the adaptive cellular response which is dependent on tumor grade and stage and treatment history [168]. There are still no preclinical models that fully recapitulate patient-specific stromal, immune, structural, chemical, and molecular aspects of the heterogeneous microenvironments to which cancer cells are sequentially exposed during the course of the disease [169]. In particular, organoids usually only contain progenitors and cells of epithelial origin, lacking other cell types such as fibroblasts, immune cells, and endothelial cells [170].…”

Section: Integrating the Microenvironment In Organoids: Current Advancesmentioning

confidence: 99%

Modeling neoplastic disease with spheroids and organoids

et al. 2020

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Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.

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Section: Integrating the Microenvironment In Organoids: Current Advancesmentioning

confidence: 99%

Modeling neoplastic disease with spheroids and organoids

et al. 2020

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“…In addition to stiffness, spatial distribution of biochemical factors can also be mediated to mimic the native tumor microenvironment. Freeform reversible embedding of suspended hydrogels (FRESH) is one of the recent techniques of EBB methods for mimicking the complex native architecture of biological tissues 18 , 19 . Employing the FRESH technique, a neuroblastoma model was developed with sodium alginate 20 .…”

Section: Introductionmentioning

confidence: 99%

3D bioprinting for reconstituting the cancer microenvironment

et al. 2020

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The cancer microenvironment is known for its complexity, both in its content as well as its dynamic nature, which is difficult to study using two-dimensional (2D) cell culture models. Several advances in tissue engineering have allowed more physiologically relevant three-dimensional (3D) in vitro cancer models, such as spheroid cultures, biopolymer scaffolds, and cancer-on-a-chip devices. Although these models serve as powerful tools for dissecting the roles of various biochemical and biophysical cues in carcinoma initiation and progression, they lack the ability to control the organization of multiple cell types in a complex dynamic 3D architecture. By virtue of its ability to precisely define perfusable networks and position of various cell types in a high-throughput manner, 3D bioprinting has the potential to more closely recapitulate the cancer microenvironment, relative to current methods. In this review, we discuss the applications of 3D bioprinting in mimicking cancer microenvironment, their use in immunotherapy as prescreening tools, and overview of current bioprinted cancer models.

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“…However, barriers to identifying effective anticancer therapies include the inability of in vitro cell culture models to recapitulate the complex three‐dimensional (3D) tumor microenvironment for screening platforms to identify therapeutic candidates . Novel complex 3D multicellular tumor models have shown promise in this application .…”

Section: Discussionmentioning

confidence: 99%

ColXα1 is a stromal component that colocalizes with elastin in the breast tumor extracellular matrix

Wang

Xiong

et al. 2018

The Journal of Pathology CR

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The tumor microenvironment regulates tissue development and homeostasis, and its dysregulation contributes to neoplastic progression. Increased expression of type X collagen α-1 (ColXα1) in tumor-associated stroma correlates with poor pathologic response to neoadjuvant chemotherapy in estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Evaluation of ColXα1 expression patterns suggests a potential connection with elastin fibers. To investigate the possible interaction between ColXα1 and elastin, we evaluated the expression of ColXα1 in relation to elastin fibers in normal breast tissue, ductal carcinoma in situ, and invasive breast carcinomas at cellular and subcellular levels. Our findings demonstrate that ColXα1 colocalizes with elastin in invasive breast cancer-associated stroma by immunohistochemistry, immunofluorescence, and electron microscopy. In 212 invasive breast carcinomas, this complex was aberrantly and selectively expressed in tumor extracellular matrix in 79% of ER+/HER2-, 80% of ER+/HER2+, 76% of ER-/HER2+, and 58% of triple negative breast cancers. In contrast, ColXα1 was generally absent, while elastin was present perivascularly in normal breast tissue. ColXα1 and elastin were coexpressed in 58% of ductal carcinoma in situ (DCIS) in periductal areas. In mass-forming DCIS with desmoplastic stroma, the complex was intensely expressed in periductal areas as well as within the tumor-associated stroma in all cases. Our data suggest that the breast carcinoma neoplastic process may involve aberrant expression of ColXα1 and elastin in the tumor microenvironment emerging early at the DCIS stage. Enrichment of these complexes in tumor-associated stroma may represent a stromal signature indicative of intrinsic differences between breast cancers. These findings shed light on investigation into the role of aberrant collagen complex expression in tumorigenesis and tumor progression which may be leveraged in therapeutic and theranostic applications.

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Engineering Breast Cancer Microenvironments and 3D Bioprinting

Cited by 90 publications

References 221 publications

Modeling neoplastic disease with spheroids and organoids

Modeling neoplastic disease with spheroids and organoids

3D bioprinting for reconstituting the cancer microenvironment

ColXα1 is a stromal component that colocalizes with elastin in the breast tumor extracellular matrix

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