Drug and radiation resistance in spheroids: cell contact and kinetics
- 1 January 1994
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cancer and Metastasis Reviews
- Vol. 13 (2), 121-138
- https://doi.org/10.1007/bf00689632
Abstract
Cells from multicellular spheroids are often more resistant than monolayers to drugs and radiation. While explanations for resistance can be based on differences in cell cycle distribution, inability of the drug to penetrate the spheroid, or the presence of hypoxic cells, these mechanisms do not adequately explain resistance to all agents. Small spheroids (containing about 25-50 cells) exposed to ionizing radiation, hyperthermia, photodynamic therapy, or topoisomerase II inhibitors, are more resistant to killing than monolayers; the close three-dimensional contact in spheroids has been implicated in this resistance. Proposed mechanisms for the 'contact effect' include gap junctional 'reciprocity', cell shape mediated changes in (repair-related) gene expression, and alterations in chromatin packaging which influence DNA repair. The consequences of the contact effect are especially important for multifraction exposures. Another form of resistance can be demonstrated during repetitive treatments; 'regrowth resistance' reflects the capacity of spheroid cells to proliferate more efficiently to compensate for cell killing.Keywords
This publication has 126 references indexed in Scilit:
- Importance of tyrosine phosphatases in the effects of cell‐cell contact and microenvironments on EGF‐stimulated tyrosine phosphorylationJournal of Cellular Physiology, 1992
- Resistance to DNA denaturation in irradiated Chinese hamster V79 fibroblasts is linked to cell shapeExperimental Cell Research, 1991
- Isolation of Chinese hamster ovary cells with reduced poly(ADP-ribose) polymerase activityMutation research. Reviews in mutation research, 1990
- Distribution and Activity of Antineoplastic Drugs in a Tumor ModelJNCI Journal of the National Cancer Institute, 1989
- Models for dose intensityMathematical Biosciences, 1988
- Increased radioresistance of cells in cultured multicell spheroidsRadiation and Environmental Biophysics, 1983
- Is there a relationship between hypoxia, contact resistance, and intercellular communication?Radiation and Environmental Biophysics, 1983
- Progressive loss of shape-responsive metabolic controls in cells with increasingly transformed phenotypeCell, 1981
- Increased radioresistance of cells in cultured multicell spheroids. I. Dependence on cellular interactionRadiation and Environmental Biophysics, 1981
- Hypothesis on Differentiation and the Inheritance of Gene SuperstructureNature, 1973