The role of decellularized cell derived extracellular matrix in the establishment and culture of in vitro breast cancer tumor model

Abstract

Decades of research have shown that 2D cell culture studies are insufficient for preclinical cancer diagnosis and treatment, and that cancer cells in 3D culture systems have better cell-cell and cell-matrix interactions, gene expression, heterogeneity, and structural complexity that more closely resemble in vivo tumors. Researchers are still optimizing 3D culturing settings for different cancers. Despite promising tumor spheroid research, tumor cell-only aggregates lack the tumor microenvironment and cannot model tumors. Here, MCF-7 breast cancer cell derived decellularized extracellular matrix (CD-dECMs) were obtained and converted into autologous, biologically active, biocompatible, and non-immunogenic hydrogels to be used as micro-environment in both organoid formation and culture. For the production of organoids, CD-dECM doping concentrations ranging from 0.1 mg/mL to 1.5 mg/mL were evaluated, and the lowest concentration was found to be the most effective. For organoid culture, 8 mg/mL CD-dECM, 4 mg/mL rat tendon collagen type I (Col I) (4 mg/mL) and a 1:1 (v/v) mixture of these two were used and the most viable and the biggest organoids were discovered in CD-dECM/Col I (1:1) group. The results show that autologous CD-dECM can replace hydrogels in tumor organoid generation and culture at low and high concentrations, respectively.

Growing Role of 3D In Vitro Cell Cultures in the Study of Cellular and Molecular Mechanisms: Short Focus on Breast Cancer, Endometriosis, Liver and Infectious Diseases

“…Currently, there is an ever-growing plethora of scientific articles reporting on the use of 3D cultures in oncological research of both so-called ‘solid’ [ 14 , 41 ] and ‘liquid’ tumors [ 42 , 43 ]. The shift from 2D in vitro systems to 3D cultures is explained by the fact that it is possible to tune these to more closely mimic in vivo tumor characteristics, including the heterogeneity of the tumor microenvironment (TME) [ 44 ], cell–cell (i.e., tumor cell–immune cell) [ 45 ] and cell–extracellular matrix contacts [ 46 ], hypoxia [ 47 ], nutrient and pH gradients [ 48 ] and biomechanical properties (such as extracellular matrix (ECM) stiffness) [ 49 ] ( Figure 1 a). This cancer-mimicking approach facilitates the study of mechanisms of cancer initiation, progression, resistance recurrence and tumour–stroma interaction, which can identify markers for early diagnosis and therapies [ 41 , 50 ].…”