Human breast cancer decellularized scaffolds promote epithelial‐to‐mesenchymal transitions and stemness of breast cancer cells in vitro

Abstract

Breast cancer, with unsatisfactory survival rates, is the leading cause of cancer‐related death in women worldwide. Recent advances in the genetic basis of breast cancer have benefitted the development of gene‐based medicines and therapies. Tissue engineering technologies, including tissue decellularizations and reconstructions, are potential therapeutic alternatives for cancer research and tissue regeneration. In our study, human breast cancer biopsies were decellularized by a detergent technique, with sodium lauryl ether sulfate (SLES) solution, for the first time. And the decellularization process was optimized to maximally maintain tissue microarchitectures and extracellular matrix (ECM) components with minimal DNA compounds preserved. Histology analysis and DNA quantification results confirmed the decellularization effect with maximal genetic compounds removal. Quantification, immunofluorescence, and histology analyses demonstrated better preservation of ECM components in 0.5% SLES‐treated scaffolds. Scaffolds seeded with MCF‐7 cells demonstrated the process of cell recellularization in vitro, with increased cell migration, proliferation, and epithelial‐to‐mesenchymal transition (EMT) process. When treated with 5‐fluorouracil, the expressions of stem cell markers, including Oct4, Sox2, and CD49F, were maximally maintained in the recellularized scaffold with decreased apoptosis rates compared with monolayer cells. These results showed that the decellularized breast scaffold model with SLES treatments would help to simulate the pathogenesis of breast cancer in vitro. And we hope that this model could further accelerate the development of effective therapies for breast cancer and benefit drug screenings.

Decellularised scaffolds: just a framework? Current knowledge and future directions

“… 99 The authors used decellularised mammary or muscle tissues isolated from nonobese diabetic (NOD)/severe combined immunodeficient (SCID) female mice (8–12 weeks old) that supported cancer cell line survival, proliferation, migration, and invasion in culture and vascularised tumour formation after implantation into the mammary fat pads of the 8-week-old female NOD/SCID mice 99 ( Figure 5 ). Another example is the work by Liu et al 100 where decellularised human breast cancer biopsies were seeded with MCF-7 breast cancer cell line showing increased cell migration, proliferation and epithelial-to-mesenchymal transition. When treated with 5-fluorouracil, an antineoplastic agent to treat multiple solid tumours including breast, expression of stem cell markers was maintained in the recellularised scaffold with decreased apoptosis rates compared to monolayer cells.…”

“…The authors concluded that the decellularised breast scaffold model would help to simulate the pathogenesis of breast cancer in vitro. 100 A last example reported by Mollica et al 101 described a novel mammary-specific culture combining a self-gelling hydrogel solely composed of decellularised rat or human breast tissue ECM with a 3D bioprinting platform. The authors were able to show that large organoids/tumoroids could be established in the mammary-derived hydrogel.…”

Decellularized Extracellular Matrix for Cancer Research

“…Thus, it is expected that the dECM that is derived from cancerous tissues is more suitable for examining the role of cancerous ECM in the regulation of cancer cell behavior at primary sites. Liu et al prepared dECM from human breast cancer tissues that were cultured with the breast cancer MCF-7 cell line [62]. In the dECM, CDH1 expression decreased during culture, while the expression of the EMT genes VIM , ZEB1 , and SNAI1 increased.…”

Tissue Engineering Models for the Study of Breast Neoplastic Disease and the Tumor Microenvironment

“…105 In terms of examples of this approach that are specific to tissue-engineered tumor models, Lü et al used decellularized tumor ECM as a 3D scaffold for tumor engineering 106 and Liu et al decellularized human breast cancer biopsies as a breast scaffold model followed by treatment with sodium lauryl ether sulfate to simulate the pathogenesis of breast cancer in vitro. 107…”