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.
Highlights
We investigated the influence of matrix on cellular behaviors by using two prostate cancer (PC) cell lines on three different matrices, and comparing cell proliferation, cellular response to anticancer drugs, and expression of drug sensitivity-associated proteins, in comparison to 2D cultured cells
We examined the expression of epidermal growth factor receptor (EGFR) and β-III tubulin in 3D- and 2D-cultured DU145 cells in an attempt to see if the expression of these proteins was influenced by the matrix type, and whether their expression was correlated with the cellular response to Rapamycin and Docetaxel
The findings in this study demonstrated that the matrix used for 3D cell cultures influenced many aspects of prostate cancer cell behavior including morphology, proliferation rate, response to chemotherapeutics, as well as the expression of proteins directly or indirectly associated with drug sensitivity
Summary
Variations in 3D culture systems most likely affect cellular behavior and may cause non-reproducible results among studies that employ different spheroid formation approaches. We investigated the influence of matrix on cellular behaviors by using two prostate cancer (PC) cell lines on three different matrices, and comparing cell proliferation, cellular response to anticancer drugs, and expression of drug sensitivity-associated proteins, in comparison to 2D cultured cells. We investigated how 3D matrices affect (1) the proliferative capacity of PC cells; (2) morphology of PC cell spheroids; (3) cellular response to two chemotherapeutic agents (Docetaxel and Rapamycin); and (4) the expression of proteins associated with drug sensitivity and their correlation with cellular response to the anti-cancer treatments
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