Abstract:
:Solid tumors consist of genetically and phenotypically diverse subpopulations of cancer cells with unique capacities for growth, differentiation, and invasion. While the molecular and microenvironmental bases for heterogeneity are increasingly appreciated, the outcomes of such intratumor heterogeneity, particularly in the context of tumor invasion and metastasis, remain poorly understood. To study heterotypic cell-cell interactions and elucidate the biological consequences of intratumor heterogeneity, we developed a tissue-engineered multicellular spheroid (MCS) co-culture model that recapitulates the cellular diversity and fully three-dimensional cell-cell and cell-matrix interactions that characterize human carcinomas. We found that "invasion-competent" malignant cells induced the collective invasion of otherwise "invasion-incompetent" epithelial cells, and that these two cell types consistently exhibited distinct leader and follower roles during invasion. Analysis of extracellular matrix (ECM) microarchitecture revealed that malignant cell invasion was accompanied by extensive ECM remodeling including matrix alignment and proteolytic track-making. Inhibition of cell contractility- and proteolysis-mediated matrix reorganization prevented leader-follower behavior and malignant cell-induced epithelial cell invasion. These results indicate that heterogeneous subpopulations within a tumor may possess specialized roles during tumor progression and suggest that complex interactions among the various subpopulations of cancer cells within a tumor may regulate critical aspects of tumor biology and affect clinical outcome.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Carey SP,Starchenko A,McGregor AL,Reinhart-King CAdoi
10.1007/s10585-013-9565-xsubject
Has Abstractpub_date
2013-06-01 00:00:00pages
615-30issue
5eissn
0262-0898issn
1573-7276journal_volume
30pub_type
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:2013-04-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF02057179
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 历史文章,杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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