Paper Info
Title
Cluster size distribution of cells disseminating from a primary tumor
Abstract
The first stage of the metastatic cascade often involves motile cells emerging from a primary tumor either as single cells or as clusters. These cells enter the circulation, transit to other parts of the body and finally are responsible for growth of secondary tumors in distant organs. The mode of dissemination is believed to depend on the EMT nature (epithelial, hybrid or mesenchymal) of the cells. Here, we calculate the cluster size distribution of these migrating cells, using a mechanistic computational model, in presence of different degree of EMT-ness of the cells; EMT is treated as given rise to changes in their active motile forces (mu) and cell-medium surface tension (Gamma). We find that, for (mu > mu(min), Gamma > 1), when the cells are hybrid in nature, the mean cluster size, N over bar similar to Gamma 2 . 0 / mu 2 . 8, where mu(min) increases with increase in Gamma. For Gamma <= 0, N over bar = 1, the cells behave as completely mesenchymal. In presence of spectrum of hybrid states with different degree of EMT-ness (motility) in primary tumor, the cells which are relatively more mesenchymal (higher mu) in nature, form larger clusters, whereas the smaller clusters are relatively more epithelial (lower mu). Moreover, the heterogeneity in mu is comparatively higher for smaller clusters with respect to that for larger clusters. We also observe that more extended cell shapes promote the formation of smaller clusters. Overall, this study establishes a framework which connects the nature and size of migrating clusters disseminating from a primary tumor with the phenotypic composition of the tumor, and can lead to the better understanding of metastasis.
Year
DOI
Venue
2021
10.1371/journal.pcbi.1009011
PLOS COMPUTATIONAL BIOLOGY
DocType
Volume
Issue
Journal
17
11
ISSN
Citations 
PageRank 
1553-734X
0
0.34
References 
Authors
0
2
Name
Order
Citations
PageRank
Mrinmoy Mukherjee100.34
Herbert Levine28212.58