Dormancy of solitary metastatic cells.
After arriving in a secondary site metastatic cells may begin proliferating, undergo apoptosis or remain as solitary dormant cells. The process of metastasis, although dangerous, is extremely inefficient with the majority of the cells undergoing apoptosis and thus becoming clinically irrelevant. Of the cells that begin proliferating, the few that make it past the micrometastasis stage may be of immediate clinical relevance. Dormant cells, while not of immediate clinical concern, are believed to be at least in part responsible for cancer recurrence that can occur decades after apparently successful initial treatment. Dormant solitary cells are different from "dormant" micrometastases, in which active proliferation is balanced by apoptosis. The mechanisms of cell cycle regulation and the function of the molecules regulating this process are well understood. However, there is relatively little known about the mechanisms controlling cell cycle regulation and dormancy of solitary metastatic cells. There are several inherent difficulties impeding the study of solitary cells. This review paper will examine the models used in the study of dormant solitary metastatic cells, methods of imaging and studying these cells, the molecular mechanisms believed to be responsible for solitary cell dormancy, and finally the unique treatment challenges posed by these cells.
Townson
Jason L
JL
Department of Medical Biophysics, University of Western Ontario and the London Regional Cancer Program, London, Ontario, Canada.
Chambers
Ann F
AF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D051379:Mice; D008853:Microscopy / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000517:prevention & control; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D013194:Staining and Labeling / Q000379:methods
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D020928:Mitogen-Activated Protein Kinases