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Breast tumour initiating cell fate is regulated by microenvironmental cues from an extracellular matrix.
MedLine Citation:
PMID:  22722498     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell-matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo complexity makes it difficult to identify parameters in a diverse milieu that affect TICs behaviour. Herein we studied how the TIC population would respond when subjected to a unique microenvironment composed of different extracellular proteins. The TIC-enriched population isolated from a Her2/neu-induced mouse mammary tumour was cultured on collagen, fibronectin and laminin coated substrates for one to two weeks. Our observations indicate that a laminin substrate can maintain the majority of the self-renewing and tumorigenic TIC population, whereas collagen induced a more differentiated phenotype of the cells. Also interestingly, fibronectin substrates dictated an invasive phenotype of TICs as evidenced from the EMT-related gene expression pattern. The results of this study signify that the microenvironmental cues play a considerable role in tumour relapse and progression by altering the cancer stem cell behaviour and thus this knowledge could be used to design novel cancer therapeutics.
Authors:
Sharmistha Saha; Pang-Kuo Lo; Xinrui Duan; Hexin Chen; Qian Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-22
Journal Detail:
Title:  Integrative biology : quantitative biosciences from nano to macro     Volume:  -     ISSN:  1757-9708     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101478378     Medline TA:  Integr Biol (Camb)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemistry and Biochemistry & Nanocenter, University of South Carolina, Columbia, SC 29208, USA. wang@mail.chem.sc.edu.
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