Abstract
Evidence is accumulating that suggests that cancer cell clusters are more likely to lead to metastatic lesions than are single cells. This mini-review explores this issue by examining evidence that indicates that cell clusters possess altered genes and metabolism that promote metastasis. When clusters are disaggregated, the resulting single cells often lose the altered properties characteristic of when they were in clusters. When cluster disrupting agents were injected into mice, metastasis was reduced. Cluster disaggregating agents are described and mechanisms of action of these compounds are explored. Using these agents to target cell clusters might offer a useful therapeutic approach in the treatment of cancer. Cell clusters are also involved in thrombocytosis and biofilm infectivity as well as cancer spread and cluster disrupting agents might be very useful in treating some human conditions in addition to cancer spread. Assays that examine the effectiveness of cluster disrupting agents are also described.
Highlights
The cellular basis of cancer metastasis is not well understood but many studies, some involving cell clusters in the metastatic process, have been reported for decades [1]
The molecular characteristics of cell clusters versus single cells are compared and how these characteristics change when clusters are disaggregated is discussed [2,3,4,5,6,7,8,9,10,11,12,13]. This mini-review will explore the issue of cell clusters as causes of metastatic lesions and new therapeutic approaches for treating cancer based on this concept are discussed
Experimental Procedure Experiments will be presented that utilize cell culture, assays that identify compounds that disaggregate cell clusters, kinetic assays that measure the effects of cell cluster disrupting agents, in vivo injections in mice, metabolic and DNA methylation assays, and statistical evaluations of results
Summary
The cellular basis of cancer metastasis is not well understood but many studies, some involving cell clusters in the metastatic process, have been reported for decades [1]. Exciting work has been more recently done exploring the issue of what is more likely to give rise to metastatic lesions, single circulating cancer cells or cell clusters [2,3,4,5,6,7,8,9,10,11,12,13]. Detailed investigations that quantitatively assess the likelihood of single cancer cells versus clusters of cancer cells in causing metastatic lesions are described [2].
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