3D bioprinting of multi-cellular tumor microenvironment for prostate cancer metastasis

Abstract

Prostate cancer (PCa) is one of the most lethal cancers in men worldwide. The tumor microenvironment (TME) plays an important role in PCa development, which consists of tumor cells, fibroblasts, endothelial cells, and extracellular matrix. Hyaluronic acid (HA) and cancer-associated fibroblasts (CAFs) are the major components in the TME and are correlated with PCa proliferation and metastasis, while the underlying mechanism is still not fully understood due to the lack of biomimetic extracellular matrix components and coculture models. In this study, gelatin methacryloyl/chondroitin sulfate-based hydrogels were physically crosslinked with HA to develop a novel bioink for the three-dimensional (3D) bioprinting of a coculture model that can be used to investigate the effect of HA on PCa behaviors and the mechanism underlying PCa-fibroblasts interaction. PCa cells demonstrated distinct transcriptional profiles under HA stimulation, where cytokine secretion, angiogenesis, and epithelial to mesenchymal transition were significantly upregulated. Further coculture of PCa with normal fibroblasts activated CAF transformation, which could be induced by the upregulated cytokine secretion of PCa cells. These results suggested HA could not only promote PCa metastasis individually but also induce PCa cells to activate CAF transformation and form HA-CAF coupling effects to further promote PCa drug resistance and metastasis.

Defining the challenges and opportunities for using patient‐derived models in prostate cancer research

“…68 Methacrylated gelatin (GelMA) has been successfully used for co-cultures of prostate cancer cells lines with cells from the TME, and for automated protocols with bioprinting. [69][70][71] Therefore, this approach holds great potential for tackling the next step of introducing patient-derived cells.…”

Microfluidics-Based Technologies for the Assessment of Castration-Resistant Prostate Cancer

“…Unlike traditional soft-lithography methods, 3D printers are used to fabricate the microfluidic devices using inorganic or polymer materials of varying chemical compositions, stiffnesses and densities [75]. In the context of prostate cancer, Xu et al (2023) [76], recently fabricated a co-culture system composed of a gelatin methacryloyl/chondroitin sulfate-based hydrogel to examine how hyaluronic acid and cancer-associated fibroblasts, two major components of the tumor microenvironment, influence prostate cancer behaviours. Both PC3 and C4-2b cells lines were used, which have been shown to represent castration-resistant tumors.…”

Preclinical Testing Techniques: Paving the Way for New Oncology Screening Approaches

“… Recent 3D bioprinted cancer models for preclinical testing using ( A – C ) breast cancer and osteoblast co-culture [ 162 ] and ( D – F ) prostate cancer and fibroblast co-culture [ 163 ]. ( A ) Schematic diagram of light-activated 3D bioprinting process using cell-laden osteoblast scaffolding seeded with breast cancer cells to model breast cancer metastasis.…”

“…Copyright 2016 American Chemical Society. ( D , E ) Reprinted under terms of the Creative Commons Attribution 4.0 License accessed on 24 August 2023 from [ 163 ].…”