Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins

Abstract

This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells. The cellular responses upon treatment with two common anti-cancer drugs, Docetaxel and Rapamycin, were examined. The expressions of epidermal growth factor receptor (EGFR) and β-III tubulin in DU145 cells and p53 in LNCaP cells were examined. The results showed that the proliferation rates of cells cultured on the three matrices varied, especially between the synthetic matrix and the biologically-derived matrices. The drug responses and the expressions of drug sensitivity-associated proteins differed between cells on various matrices as well. Among the 3D cultures on the three matrices, increased expression of β-III tubulin in DU145 cells was correlated with increased resistance to Docetaxel, and decreased expression of EGFR in DU145 cells was correlated with increased sensitivity to Rapamycin. Increased expression of a p53 dimer in 3D-cultured LNCaP cells was correlated with increased resistance to Docetaxel. Collectively, the results showed that the matrix of 3D cell culture models strongly influences cellular behaviors, which highlights the imperative need to achieve standardization of 3D cell culture technology in order to be used in drug screening and cell biology studies.

Assessing the effect of triethyleneglycol dimethacrylate on tissue repair in 3D organotypic cultures

“…Our data demonstrating the capability of viable GFs treated with high concentrations of TEGDMA to interact into 3D constructs versus their high mortality rate in 2D cultures highlighting the importance in the involvement of the 3D cell‐based ECM platform in the screening process of innovative materials and/or drugs. Studies performed on various cancer cells treated with anticancer drugs revealed a higher rate of survival for 3D‐matrigel versus 2D cultures (Edmondson, Adcock, & Yang, ). However, it should also be noted that the resistance is dependent on the cell type as no structural organization of DPMCs was observed at similar concentrations of TEGDMA (data not shown).…”

Development and cytotoxic response of two proliferative MDA-MB-231 and non-proliferative SUM1315 three-dimensional cell culture models of triple-negative basal-like breast cancer cell lines

“…This could be explained by a proliferative capacity of the MDA-MB-231 cell line under these experimental conditions in comparison to the SUM1315 cell line that may exhibit a "stem-cell like" phenotype with slowed down proliferation rate [23]. In 3D culture models, cells forming spheroids may or may not proliferate according to cell type and the extracellular matrix environment [24,25]. Nevertheless, in both TNBL 3D cell cultures, spheroid diameters did not exceed 1000 μm, which could be explained by the fact that the spheroids had reached their growth plateau [19].…”

ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression

“…Microtubules are dynamically regulated by polymerization and depolymerization, and their mechanical properties determine their own shape and strength . Besides, βIII‐tubulin protein that is encoded by TUBB3 is upregulated in prostate cancer cells under 3D culture conditions compared to 2D culture condition and elevated expression of βIII‐tubulin may associate with the resistance to microtubule inhibitor docetaxel . Thus, TUBB3 may contribute to spheroid formation of bladder CSCs through modulating microtubule activity.…”