Linked Life Data

12036948

Source:http://linkedlifedata.com/resource/pubmed/id/12036948

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-5-30
pubmed:abstractText
Reactive stroma has been reported in many cancers, including breast, colon,and prostate. Although changes in stromal cell phenotype and extracellular matrix have been reported, specific mechanisms of how reactive stroma affects tumor progression are not understood. To address the role of stromal cells in differential regulation of tumor incidence, growth rate, and angiogenesis, LNCaP xenograft tumors were constructed in nude mice with five different human prostate stromal cell lines as well as GeneSwitch-3T3 cells engineered to express lacZ under mifepristone regulation. Alone, LNCaP prostate carcinoma cells were essentially nontumorigenic, whereas combinations of LNCaP cells with three different human prostate stromal cell lines (L/S tumors) resulted in a tumor incidence (50-63%) similar to that of control LNCaP plus Matrigel (L/M) tumors over a 9-week period. In contrast, LNCaP combinations with two other human prostate stromal cell lines were nontumorigenic, illustrating that stromal cell effects are differential. L/S tumors exhibited well-developed blood vessels at 2 weeks, whereas control L/M tumors were avascular at 2 weeks and exhibited blood lakes in lieu of extensive vessels at later time points. Xenografts constructed under three-way conditions (LNCaP, Matrigel, and stromal cells; L/M/S tumors) exhibited a 100% tumor incidence and showed rapid blood vessel formation as early as day 7 with mature vessels formed by day 10. L/M/S tumors exhibited a 10.3-fold increase in microvessel density, and the corresponding hemoglobin:tumor weight ratio was increased 2-fold relative to L/M control tumors at day 10. L/M/S tumor wet weight and volume increased by 1.6- and 2.4-fold, respectively, by day 21, compared with control L/M tumors. L/M/S tumors made with LNCaP cells plus GeneSwitch-3T3-pGene/lacZ stromal cells showed similar results. Mifepristone-regulated gene expression was observed in stromal cells immediately adjacent to clusters of carcinoma cells and in vessel walls in a mural cell (pericyte) position. This study shows that regulation of angiogenesis is one mechanism through which stromal cells affect LNCaP tumor incidence and growth rate. This regulation may be mediated through direct recruitment and interactions of stromal cells with endothelial cells. Furthermore, this study describes for the first time a model system with regulated transgene expression in the stromal compartment of an experimental carcinoma. These findings point to the stromal compartment as a potential source of new prognostic markers and therapeutic targets and show the utility of the carcinoma-stromal xenograft model system in dissecting specific mechanisms of reactive stroma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3298-307
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model.
pubmed:affiliation
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't