Document Detail

Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.
MedLine Citation:
PMID:  23359139     Owner:  NLM     Status:  MEDLINE    
Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and β-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.
Raghu Kadaba; Hanna Birke; Jun Wang; Steven Hooper; Claudia D Andl; Francesco Di Maggio; Erdinc Soylu; Mohammed Ghallab; Daniel Bor; Fieke Em Froeling; Satyajit Bhattacharya; Anil K Rustgi; Erik Sahai; Claude Chelala; Peter Sasieni; Hemant M Kocher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-03-21
Journal Detail:
Title:  The Journal of pathology     Volume:  230     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-13     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  107-17     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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MeSH Terms
Apoptosis / physiology
Cell Line, Tumor
Cell Survival / physiology
Disease Progression
Epithelial Cells / metabolism,  pathology
Extracellular Matrix / pathology*
Gene Expression Regulation, Neoplastic / physiology
Myofibroblasts / metabolism,  pathology
Neoplasm Invasiveness / pathology
Organ Culture Techniques
Pancreas / pathology*
Pancreatic Neoplasms / genetics,  metabolism,  pathology*
Pancreatic Stellate Cells / metabolism,  pathology
Signal Transduction / physiology
Stromal Cells / metabolism,  pathology*
Tissue Array Analysis
Grant Support
15154//Cancer Research UK; DK075379/DK/NIDDK NIH HHS; K01 DK075379/DK/NIDDK NIH HHS; P01 CA098101/CA/NCI NIH HHS; P01-CA098101/CA/NCI NIH HHS; P30 CA016520/CA/NCI NIH HHS; //Cancer Research UK
Comment In:
J Pathol. 2013 Sep;231(1):4-7   [PMID:  23716361 ]

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