Multicellular tumor spheroids

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The term multicellular tumor spheroids also tumor spheroids , spheroids - (from English : "multicellular tumor spheroids", MCTS ) stands in cell biology for spherical aggregates that arise from several thousand tumor cells .

Multicellular tumor spheroids are used in cell culture laboratories as in-vitro models for studying tumor diseases and for establishing new therapeutic approaches.

history

At the beginning of the 20th century, Holtfreter and later Moscana did the pioneering work in their studies on spherical aggregates , which arose from isolated embryo and malignant cells . Sutherland and colleagues later described the first radiation tests on MCTS and established them as an in vitro model for systematic studies on tumor cells.

Generation

Malignant cell lines are often characterized by the fact that they can form multicellular spheroids. Spheroids can be generated by sowing a suspension of cells on an agarose- coated Petri dish. After a few days, several small tumor spheroids form, but they have different diameters and must be separated according to size. In order to ensure a uniform spheroid size, equal volumes of tumor cell suspensions are pipetted into agarose-coated wells of a microtiter plate in an alternative test arrangement. Ultimately, only one spheroid is formed per well at the deepest point of the curvature of those agarose surfaces. Furthermore, after initiation, spheroids can also be transferred to spinner bottles , which ensures a better supply of nutrients and oxygen to the cells. Some cell lines can also form spheroids directly from a cell suspension cultivated in spinner bottles.

properties

MCTS have a spherical structure. The rate of proliferation of the cells in a spheroid correlates with the availability of nutrients and oxygen . The outer layer of the spheroid consists of proliferating tumor cells. The middle layer is made up of cells that are in the G0 phase . Due to the gradients of nutrients, metabolites and oxygen falling towards the center, central necrosis develops in the vicinity of the center.

MCTS in action

MCTS imitate mini-metastases and areas of solid tumors in vivo , and thus represent a more complex model, more similar to the in vivo situation, than monolayer cell cultures and suspension cell cultures for a large number of areas of application in tumor cell research . MCTS are becoming increasingly important in physiology and cell biology , as well as in immunology , molecular biology and neurophysiology . Compared to xenograft models, MCTS enable a high throughput rate of tests due to a well controllable test setup with a large number of pieces. The in vitro model provides extensive knowledge about the expression behavior, signal transduction and metabolism of a cell line in a three-dimensional cell structure. A wide range of potential anti-tumor therapeutics can be tested for effectiveness with MCTS. Examples are natural substance extracts from green tea. Likewise, macromolecules can e.g. B. in the form of polymeric nanoparticles can be examined for their cytotoxic behavior towards tumor spheroids. MCTS are also increasingly playing a key role in tumor immunology. The efficiency of therapeutic antibodies in activating the immune system can be examined if they are cocultivated with MCTS and PBMCs (from English : "Peripheral Blood Mononuclear Cell " ).

swell

  1. ^ Wolfgang Mueller-Klieser: Three-dimensional cell cultures. From molecular mechanisms to clinical applications. In: American Journal of Physiology-Cell Physiology . 1997; 273: C1109-C1123, PMID 9357753
  2. ↑ J. Holtfreter et al .: A study of the mechanism of gastrulation. In: Journal of Experimental Zoology. Volume 95, 1944, pp. 171-212.
  3. ^ A. Moscona et al .: The development in vitro of chimeric aggregates of dissociated embryonic chick and mouse cells. In: Proceedings of the National Academy of Sciences . Volume 57, 1952, pp. 184-194. PMID 16589996
  4. ^ RE Durand and RM Sutherland: Radiation studies with spheroids. In: Recent Results Cancer Res. Volume 95, 1984, p. 103, PMID 6396754
  5. ↑ RM Sutherland and RE Durand: Growth and cellular characteristics of multicell spheroids. In: Recent Results Cancer Res. Volume 95, 1984, pp. 24-49, PMID 6396760
  6. ^ W. Mueller-Klieser, JP Freyer and RM Sutherland: Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids. In: British Journal of Cancer . Volume 53, 1986, pp. 345-353, PMID 3964538
  7. ^ LA Kunz-Schughart, JP Freyer, F. Hofstaedter and R. Ebner: The use of 3-D cultures for high-throughput screening: the multicellular spheroid model. In: Journal of Biomolecular Screening . Volume 9, 2004, pp. 273-285, PMID 15191644
  8. ^ Stefan Walenta, Joerg Doetsch, Wolfgang Mueller-Klieser, Leoni A. Kunz-Schughart: Metabolic imaging in multicellular spheroids of oncogene-transfected fibroblasts. In: Journal of Histochemistry and Cytochemistry. Volume 48, 2000, pp. 509-522, PMID 10727293
  9. ^ W. Mueller-Klieser, S. Schreiber-Klais, S. Walenta, MH Kreuter: Bioactivity of well-defined green tea extracts in multicellular tumor spheroids. In: International Journal of Oncology . Volume 21, 2002, pp. 1307-1315 PMID 12429982
  10. ^ G. Fracasso and M. Colombatti: Effect of therapeutic macromolecules in spheroids. In: Critical Reviews in Oncology Hematology . Volume 36, 2000, pp. 159-178, PMID 11033304
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