The Use of Human Tumor Cells Grown in Multicellular Spheroid Culture for Designing and Improving Therapeutic Strategies

Acker, H.

doi:10.1080/10273669808833019

Cited by 6 publications

(2 citation statements)

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“…These pressure effects, as an inhibiting factor of tumor cell proliferation, are in good agreement with previous reports on solid state stress in tumor spheroids (Haji-Karim and Carlsson, 1978;Mueller-Klieser, 1997;Acker, 1998;Hamilton, 1998;Kunz-Schugart et al, 1998;Santini and Rainaldi, 1999). These spheroids are clusters of cancer cells that have been widely used in the laboratory to study the early stages of avascular tumor growth, the response to external factors such as supplied nutrients or growth inhibitory factors, cellular differentiation, and cell-cell interactions, and have even been used in therapeutically oriented studies.…”

Section: Discussionsupporting

confidence: 92%

The Universal Dynamics of Tumor Growth

Brú

Albertos

Subiza

et al. 2003

Biophysical Journal

367

265

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Scaling techniques were used to analyze the fractal nature of colonies of 15 cell lines growing in vitro as well as of 16 types of tumor developing in vivo. All cell colonies were found to exhibit exactly the same growth dynamics-which correspond to the molecular beam epitaxy (MBE) universality class. MBE dynamics are characterized by 1), a linear growth rate, 2), the constraint of cell proliferation to the colony/tumor border, and 3), surface diffusion of cells at the growing edge. These characteristics were experimentally verified in the studied colonies. That these should show MBE dynamics is in strong contrast with the currently established concept of tumor growth: the kinetics of this type of proliferation rules out exponential or Gompertzian growth. Rather, a clear linear growth regime is followed. The importance of new cell movements-cell diffusion at the tumor border-lies in the fact that tumor growth must be conceived as a competition for space between the tumor and the host, and not for nutrients or other factors. Strong experimental evidence is presented for 16 types of tumor, the growth of which cell surface diffusion may be the main mechanism responsible in vivo. These results explain most of the clinical and biological features of colonies and tumors, offer new theoretical frameworks, and challenge the wisdom of some current clinical strategies.

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Section: Discussionsupporting

confidence: 92%

The Universal Dynamics of Tumor Growth

Brú

Albertos

Subiza

et al. 2003

Biophysical Journal

367

265

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“…For example, in spheroid models of colorectal cancer [33] and pancreatic cancer [34], a reduction in the responsiveness to antitumour agents was observed as a function of multicellular 3D architecture. Multicellular drug resistance is not a new concept and has been studied for the past three decades [35][36][37][38][39][40][41][42]. It is associated with the ability of 3D tumour spheroids from human cancer cell lines to mimic cell dormancy [43,44].…”

Section: Introductionmentioning

confidence: 99%

Nanotoxicity in Cancer Research: Technical Protocols and Considerations for the Use of 3D Tumour Spheroids

Movia¹,

Prina‐Mello²

2018

Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications

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The poor clinical translation of oncological nanomedicine products is one of the greatest challenges faced by research today. The use of reductionist in vitro models of human cancer and non-predictive animal models is generally considered as one of the main causes of such very low translation rate. The integration of three-dimensional (3D) tumour spheroids in the early stages of the preclinical screening pipeline could significantly facilitate the translation of nanomedicine candidates into clinical practice, by allowing for a more reliable prediction of their efficacy and safety in humans. To lead a successful integration of 3D spheroids, protocols that satisfy issues of ease-of-use, reproducibility and compatibility with conventional and high-throughput assays, without losing the advantages offered by two-dimensional (2D) cell systems, are still needed. To address such need, protocols for the formation and characterisation of scaffold-free 3D tumour spheroids of human adenocarcinoma cells were developed and optimised in this study for their application in nanomedicine safety testing. The protocols reported in this chapter provide the ground on how 3D tumour spheroids could be implemented to design nanomedicine products and speed up experimental cancer research, eliminating those candidates that are likely to be ineffective or unsafe in human at early development stages.

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