Characterization of a new model of human prostatic cancer: The multicellular tumor spheroid

Jt, Donaldson; Ja, Tucker; Te, Keane; Pj, Walther; Ks, Webb

doi:10.1002/ijc.2910460216

Cited by 15 publications

(5 citation statements)

References 13 publications

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“…In this phase, total cell concentrations increased only threefold: a specific growth rate 1/10th of that published by our lab for DU 145 cells in monolayer culture (Clejan et al, 1996). This apparent reduction in cellular growth rate is, however, typical of the ripening phase in spheroidal systems where only the outermost cell layers proliferate (Donaldson et al, 1990;Yuhas and Li, 1978). The initial rapid increase in spheroid size was then not a function of internal cellular growth, but entirely due to coalescence among free cells and aggregates during the first 72 h of culture.…”

Section: Overview Of Spheroid Developmentmentioning

confidence: 70%

Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human prostate cancer cells

Enmon

O’Connor

Lacks

et al. 2001

Biotechnol. Bioeng.

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The in vitro self‐assembly of multicellular spheroids generates highly organized structures in which the three‐dimensional structure and differentiated function frequently mimic that of in vivo tissues. This has led to their use in such diverse applications as tissue regeneration and drug therapy. Using Smoluchowski‐like rate equations, herein we present a model of the self‐aggregation of DU 145 human prostate carcinoma cells in liquid‐overlay culture to elucidate some of the physical parameters affecting homotypic aggregation in attachment‐dependent cells. Experimental results indicate that self‐aggregation in our system is divided into three distinct phases: a transient reorganization of initial cell clusters, an active aggregation characterized by constant rate coefficients, and a ripening phase of established spheroid growth. In contrast to the diffusion‐controlled aggregation previously observed for attachment‐independent cells, the model suggests that active aggregation in our system is reaction‐controlled. The rate equations accurately predict the aggregation kinetics of spheroids containing up to 30 cells and are dominated by spheroid adhesive potential with lesser con‐ tributions from the radius of influence. The adhesion probability increases with spheroid size so that spheroid–spheroid adhesions are a minimum of 2.5 times more likely than those of cell–cell, possibly due to the upregulation of extracellular matrix proteins and cell‐adhesion molecules. The radius of influence is at least 1.5 to 3 times greater than expected for spherical geometry as a result of ellipsoidal shape and possible chemotactic or Fröhlich interactions. Brownian‐type behavior was noted for spheroids larger than 30 μm in diameter, but smaller aggregates were more motile by as much as a factor of 10 for single cells. The model may improve spheroid fidelity for existing applications of spheroids and form the basis of a simple assay for quantitatively evaluating cellular metastatic potential as well as therapies that seek to alter this potential. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 72: 579–591, 2001.

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Section: Overview Of Spheroid Developmentmentioning

confidence: 70%

Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human prostate cancer cells

Enmon

O’Connor

Lacks

et al. 2001

Biotechnol. Bioeng.

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“…This approach directly revealed in-depth topography of the 3D cultures at nanoscale resolution, which clearly resembled in vivo tumor-like morphology. [17][18][19] Two-photon or multiphoton microscopy is fundamentally different from traditional linear excitation microscopy. Multiphoton microscopy uses higher-order light-matter interactions involving multiple photons for contrast generation.…”

Section: Discussionmentioning

confidence: 99%

Multicellular Tumor Spheroids as an in Vivo–Like Tumor Model for Three-Dimensional Imaging of Chemotherapeutic and Nano Material Cellular Penetration

et al. 2012

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We present a flexible and highly reproducible method using three-dimensional (3D) multicellular tumor spheroids to quantify chemotherapeutic and nanoparticle penetration properties in vitro. We generated HeLa cell-derived spheroids using the liquid overlay method. To properly characterize HeLa spheroids, scanning electron microscopy, transmission electron microscopy, and multiphoton microscopy were used to obtain high-resolution 3D images of HeLa spheroids. Next, pairing high-resolution optical characterization techniques with flow cytometry, we quantitatively compared the penetration of doxorubicin, quantum dots, and synthetic micelles into 3D HeLa spheroid versus HeLa cells grown in a traditional two-dimensional culturing system. Our data revealed that 3D cultured HeLa cells acquired several clinically relevant morphologic and cellular characteristics (such as resistance to chemotherapeutics) often found in human solid tumors. These characteristic, however, could not be captured using conventional two-dimensional cell culture techniques. This study demonstrated the remarkable versatility of HeLa spheroid 3D imaging. In addition, our results revealed the capability of HeLa spheroids to function as a screening tool for nanoparticles or synthetic micelles that, due to their inherent size, charge, and hydrophobicity, can penetrate into solid tumors and act as delivery vehicles for chemotherapeutics. The development of this image-based, reproducible, and quantifiable in vitro HeLa spheroid screening tool will greatly aid future exploration of chemotherapeutics and nanoparticle delivery into solid tumors.

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“…Multicellular spheroids Liquid-overlay technique was used to obtain the spheroids (8)(9)(10). In short, tissue culture dishes were coated with 0.5 mL of 1% agarose (Sigma, St Louis, USA) that was boiled in sterile RPMI-1640 without serum.…”

Section: Growth On Flexible Supportmentioning

confidence: 99%

Mode of Growth Determines Differential Expression of Prostasomes in Cultures of Prostate Cancer Cell Lines and Opens for Studies of Prostasome Gene Expression

Carlsson

Lennartsson

Ronquist

et al. 2006

Upsala Journal of Medical Sciences

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The exocrine secretion of the acinar gland cells in the human prostate consists of, among other components, a serous secretion and prostasomes. The prostasomes are functionally associated with both reproduction and prostate cancer development and are capable to raise autoantibodies at various pathologies. Therefore, we are trying to characterize prostasome antigens by analysing prostasome-producing cell lines of prostate cancers with the cDNA microarray technique. To obtain one state with synthesis of prostasomes and another state without synthesis, we checked whether the prostasome differentiation was influenced by the mode of growing the cells, that is, whether the cells had been growing on a solid support or on a flexible one.We studied the expression of prostasomes in the cell lines PC3, DU145 and LNCaP. We grew the cells with the following methods: Monocellular layers on microbeads, multicellular spheroids, single cells in suspension cultures, and xenotransplants in nude rats. The presence of prostasomes was examined by ELISA, immunocytochemistry or electron microscopy.The results showed that growing the cells on microbeads (solid support) produced a differentiation of prostasomes, while growing the cells in multicellular spheroids (flexible support) did not. Thus it should be possible to apply cDNA microarray analyses for characterizing the genes which are active at the cellular expression of prostasomes and then deduce the prostasome antigens.

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Characterization of a new model of human prostatic cancer: The multicellular tumor spheroid

Cited by 15 publications

References 13 publications

Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human prostate cancer cells

Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human prostate cancer cells

Multicellular Tumor Spheroids as an in Vivo–Like Tumor Model for Three-Dimensional Imaging of Chemotherapeutic and Nano Material Cellular Penetration

Mode of Growth Determines Differential Expression of Prostasomes in Cultures of Prostate Cancer Cell Lines and Opens for Studies of Prostasome Gene Expression

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