Tunable three-dimensional engineered prostate cancer tissues for in vitro recapitulation of heterogeneous in vivo prostate tumor stiffness

Habbit, Nicole L.; Anbiah, Benjamin; Anderson, Luke; Suresh, Joshita; Hassani, Iman; Eggert, Matthew; Brannen, Andrew; Davis, Joshua; Tian, Yuan; Prabhakarpandian, Balabhaskar; Panizzi, Peter; Arnold, Robert D.; Lipke, Elizabeth A.

doi:10.1016/j.actbio.2022.05.011

Cited by 3 publications

(8 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate CRPC‐ne and fibroblast cell‐cell interactions within a 3D, biomechanically‐relevant [ 26 ] engineered microenvironment, PC‐3 cancer cells and BJ‐5ta human fibroblasts were encapsulated in PF at a concentration of 20 × 10 6 cells mL −1 both individually in monoculture and in coculture at cancer to fibroblast cell ratios of 5:1, 1:1 and 1:5 (Figure 1A). Regardless of initial cell population ratio, greater than 95% of cells survived the encapsulation process ( n = 3 EPCaTs from separately prepared batches per condition, p ≤ 0.05); similarly high viability (> 96%, n = 3 EPCaTs from separately prepared batches per condition, p ≤ 0.05) was maintained over 15 days of in vitro coculture in cancer cell‐specific media (Figure 1B,C).…”

Section: Resultsmentioning

confidence: 99%

“…PF Synthesis and Characterization: PF was synthesized in-house according to a previously reported protocol. [26,41] Briefly, bovine fibrinogen was dissolved to a final concentration of 7 mg mL −1 in an 8 m urea in 10 mm phosphate buffered saline (PBS) solution. Synthesized PEGDA [26,42] (10 kDa, >99% acrylation) was also dissolved in an 8 m urea-PBS buffer solution at a final concentration of 280 mg mL −1 ; vortex and centrifugation at 2500 RPM for 3 min were employed to clear the solution.…”

Section: Methodsmentioning

confidence: 99%

“…[26,41] Briefly, bovine fibrinogen was dissolved to a final concentration of 7 mg mL −1 in an 8 m urea in 10 mm phosphate buffered saline (PBS) solution. Synthesized PEGDA [26,42] (10 kDa, >99% acrylation) was also dissolved in an 8 m urea-PBS buffer solution at a final concentration of 280 mg mL −1 ; vortex and centrifugation at 2500 RPM for 3 min were employed to clear the solution. Tris (2-carboxyethyl) Phosphine Hydrochloride (TCEP-HCl) was added to the fibrinogen solution at a 1.5:1 molar ratio to the fibrinogen cysteines; subsequently, the pH of the solution was adjusted to 8.0.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we report an in vitro 3D engineered prostate cancer tissue (EPCaT) model comprised of either CRPC or ADPC prostate cancer cell lines in direct coculture with human fibroblasts within a bioinspired, [ 26 ] enzymatically cleavable poly(ethylene glycol)‐fibrinogen (PF) matrix. To simultaneously model a highly aggressive, neuroendocrine variant of metastatic CRPC (CRPC‐ne) and investigate the impact of cancer cell to fibroblast cell ratio on PCa cell behavior, PC‐3 prostate cancer cells were encapsulated in monoculture and in coculture with human BJ‐5ta normal fibroblasts at cancer to stromal cell ratios of 5:1, 1:1, and 1:5.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ratiometric Inclusion of Fibroblasts Promotes Both Castration‐Resistant and Androgen‐Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues

Habbit

Anbiah

Suresh

et al. 2023

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

To investigate the ratiometric role of fibroblasts in prostate cancer (PCa) progression, this work establishes a matrix‐inclusive, three‐dimensional engineered prostate cancer tissue (EPCaT) model that enables direct coculture of neuroendocrine‐variant castration‐resistant (CPRC‐ne) or androgen‐dependent (ADPC) PCa cells with tumor‐supporting stromal cell types. Results show that the inclusion of fibroblasts within CRPC‐ne and ADPC EPCaTs drives PCa aggression through significant matrix remodeling and increased proliferative cell populations. Interestingly, this is observed to a much greater degree in EPCaTs formed with a small number of fibroblasts relative to the number of PCa cells. Fibroblast coculture also results in ADPC behavior more similar to the aggressive CRPC‐ne condition, suggesting fibroblasts play a role in elevating PCa disease state and may contribute to the ADPC to CRPC‐ne switch. Bulk transcriptomic analyses additionally elucidate fibroblast‐driven enrichment of hallmark gene sets associated with tumorigenic progression. Finally, the EPCaT model clinical relevancy is probed through a comparison to the Cancer Genome Atlas (TCGA) PCa patient cohort; notably, similar gene set enrichment is observed between EPCaT models and the patient primary tumor transcriptome. Taken together, study results demonstrate the potential of the EPCaT model to serve as a PCa‐mimetic tool in future therapeutic development efforts.This article is protected by copyright. All rights reserved

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ratiometric Inclusion of Fibroblasts Promotes Both Castration‐Resistant and Androgen‐Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues

Habbit

Anbiah

Suresh

et al. 2023

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…The use of 3D cancer cell culture, including both scaffold-free and scaffold-based 3D models, has been reported for breast cancer, [4][5][6][7][8][9][10][11] prostate cancer, [12][13][14][15][16][17][18][19] lung cancer, 20,21 colorectal cancer, [22][23][24][25][26][27][28][29][30] and melanoma 31 among others. Self-aggregated tumor spheroids (TS) and organoids, valuable scaffold-free 3D cancer models, have been successfully employed in colorectal cancer research.…”

mentioning

confidence: 99%

Establishment of a tissue‐engineered colon cancer model for comparative analysis of cancer cell lines

Hassani,

Anbiah,

Moore

et al. 2023

J Biomedical Materials Res

Self Cite

View full text Add to dashboard Cite

To overcome the limitations of in vitro two‐dimensional (2D) cancer models in mimicking the complexities of the native tumor milieu, three‐dimensional (3D) engineered cancer models using biomimetic materials have been introduced to more closely recapitulate the key attributes of the tumor microenvironment. Specifically, for colorectal cancer (CRC), a few studies have developed 3D engineered tumor models to investigate cell–cell interactions or efficacy of anti‐cancer drugs. However, recapitulation of CRC cell line phenotypic differences within a 3D engineered matrix has not been systematically investigated. Here, we developed an in vitro 3D engineered CRC (3D‐eCRC) tissue model using the natural‐synthetic hybrid biomaterial PEG‐fibrinogen and three CRC cell lines, HCT 116, HT‐29, and SW480. To better recapitulate native tumor conditions, our 3D‐eCRC model supported higher cell density encapsulation (20 × 106 cells/mL) and enabled longer term maintenance (29 days) as compared to previously reported in vitro CRC models. The 3D‐eCRCs formed using each cell line demonstrated line‐dependent differences in cellular and tissue properties, including cellular growth and morphology, cell subpopulations, cell size, cell granularity, migration patterns, tissue growth, gene expression, and tissue stiffness. Importantly, these differences were found to be most prominent from Day 22 to Day 29, thereby indicating the importance of long‐term culture of engineered CRC tissues for recapitulation and investigation of mechanistic differences and drug response. Our 3D‐eCRC tissue model showed high potential for supporting future in vitro comparative studies of disease progression, metastatic mechanisms, and anti‐cancer drug candidate response in a CRC cell line‐dependent manner.

show abstract

Current Advances in the Use of Tissue Engineering for Cancer Metastasis Therapeutics

Katti,

Jasuja

2024

Polymers

View full text Add to dashboard Cite

Cancer is a leading cause of death worldwide and results in nearly 10 million deaths each year. The global economic burden of cancer from 2020 to 2050 is estimated to be USD 25.2 trillion. The spread of cancer to distant organs through metastasis is the leading cause of death due to cancer. However, as of today, there is no cure for metastasis. Tissue engineering is a promising field for regenerative medicine that is likely to be able to provide rehabilitation procedures to patients who have undergone surgeries, such as mastectomy and other reconstructive procedures. Another important use of tissue engineering has emerged recently that involves the development of realistic and robust in vitro models of cancer metastasis, to aid in drug discovery and new metastasis therapeutics, as well as evaluate cancer biology at metastasis. This review covers the current studies in developing tissue-engineered metastasis structures. This article reports recent developments in in vitro models for breast, prostate, colon, and pancreatic cancer. The review also identifies challenges and opportunities in the use of tissue engineering toward new, clinically relevant therapies that aim to reduce the cancer burden.

show abstract

Tunable three-dimensional engineered prostate cancer tissues for in vitro recapitulation of heterogeneous in vivo prostate tumor stiffness

Cited by 3 publications

References 60 publications

Ratiometric Inclusion of Fibroblasts Promotes Both Castration‐Resistant and Androgen‐Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues

Ratiometric Inclusion of Fibroblasts Promotes Both Castration‐Resistant and Androgen‐Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues

Establishment of a tissue‐engineered colon cancer model for comparative analysis of cancer cell lines

Current Advances in the Use of Tissue Engineering for Cancer Metastasis Therapeutics

Contact Info

Product

Resources

About