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PMID: 21556134 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Solving the puzzle of metastasis: the evolution of cell migration in neoplasms.

PloS one ·Vol. 6 ·No. 4 ·2011-04-27 ·Pages e17933

Chen J, Sprouffske K, Huang Q, Maley CC

Abstract

Metastasis represents one of the most clinically important transitions in neoplastic progression. The evolution of metastasis is a puzzle because a metastatic clone is at a disadvantage in competition for space and resources with non-metastatic clones in the primary tumor. Metastatic clones waste some of their reproductive potential on emigrating cells with little chance of establishing metastases. We suggest that resource heterogeneity within primary tumors selects for cell migration, and that cell emigration is a by-product of that selection. We developed an agent-based model to simulate the evolution of neoplastic cell migration. We simulated the essential dynamics of neoangiogenesis and blood vessel occlusion that lead to resource heterogeneity in neoplasms. We observed the probability and speed of cell migration that evolves with changes in parameters that control the degree of spatial and temporal resource heterogeneity. Across a broad range of realistic parameter values, increasing degrees of spatial and temporal heterogeneity select for the evolution of increased cell migration and emigration. We showed that variability in resources within a neoplasm (e.g. oxygen and nutrients provided by angiogenesis) is sufficient to select for cells with high motility. These cells are also more likely to emigrate from the tumor, which is the first step in metastasis and the key to the puzzle of metastasis. Thus, we have identified a novel potential solution to the puzzle of metastasis.

MeSH Terms
Blood Vessels/pathology Cell Movement Humans Models, Theoretical Neoplasm Metastasis Neoplasms/blood supply,pathology Neovascularization, Pathologic
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chen Jun
Genomics and Computational Biology Program, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Sprouffske Kathleen
Huang Qihong
Maley Carlo C
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0017933
Published
2011-04-27
Epub
2011-00-27
Pages
e17933
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3083389
Subset
IM
Grants
NCI NIH HHS · P30 CA010815 · United States
NINDS NIH HHS · R21 NS059478 · United States
NCI NIH HHS · R01CA148759 · United States
NCI NIH HHS · R03 CA137811 · United States
NCI NIH HHS · R01 CA140657 · United States
NCI NIH HHS · R01 CA119224 · United States
NCI NIH HHS · R01 CA148759 · United States
NCI NIH HHS · P01 CA091955 · United States
NCI NIH HHS · P01 CA91955 · United States
NHGRI NIH HHS · T32 HG000046 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0017933 PMC Full Text View journal details
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