Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis

The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics

“…In general, the trend in all 3D cell culture models (CollGAG, S200 and S500) towards higher PSA secretion, however, correlates with increased pathogenesis. Previously, it has been reported that LNCaP cells co-cultured with primary human osteoblasts demonstrated elevated PSA levels even in the absence of androgen stimulation [28]. This is similar to the results obtained in this study by 3D LNCaP monoculture and suggests an improved physiological relevance relative to 2D cell culture.…”

“…By contrast, the androgen dependent LNCaP cell line is known to express PSA [70] which can be further induced in the presence of androgens [28,72]. Hence the ability of LNCaP cells cultured in 3D on the three collagen-based scaffolds (CollGAG, S200 and S500) to enhance PSA secretion in the absence of androgen stimulation was investigated.…”

“…They have been widely investigated for tissue engineering applications [21] and such scaffolds have been specifically optimised for bone repair [22e25], focusing on the restoration of form and function of tissue insufficiencies [26]. In addition, the use of such scaffolds for the in vitro culture of cells in a 3D environment is now recognised to offer potential to enhance our understanding of disease mechanisms and pathology with a resulting improvement in treatment outcomes [15,17,27,28].…”

Osteoblastic and osteoclastic differentiation of human mesenchymal stem cells and monocytes in a miniaturized three-dimensional culture with mineral granules

“…Various normal cells and the ECM may be implicated in tumour development or in the drug resistance of tumour cells [38,39]. The present 3-D constructs, where numerous cell types, including tumour cells may be cultured on an abundant osteoid matrix with BCP particles, may help in the development of new oncology drugs and decrease drug failure during clinical testing [7,40,41]. In this miniaturized 3-D model, a 90-day culture time is not required for drug screening as the collagen matrix is produced within 3 days and it can support tumour cell growth.…”

Hydrogels and bioreactors for cartilage research and functional tissue engineering

“…Other approaches include the combined silk-collagen scaffolds developed by the Kaplan group [298] to build a brain-like tissue, in which the biphasic architecture enables the spatially controlled growth of a neuronal network, thus mimicking the 3D morphology of the brain cortex. Other scaffold technology platforms enable researchers to monitor oxygen levels and determine hypoxia in a 3D cell culture setup [299], as well as to investigate mechanisms that are altered during bone metastasis in patients with prostate cancer [300].…”