Linked Life Data

16152579

Source:http://linkedlifedata.com/resource/pubmed/id/16152579

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-2-1
pubmed:abstractText
The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd-Ecad). Three-dimensional human tissue constructs harboring either H-2Kd-Ecad-expressing or control II-4 cells (pBabe, H-2Kd-EcadDeltaC25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd-Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 gamma2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
821-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16152579-Animals, pubmed-meshheading:16152579-Cadherins, pubmed-meshheading:16152579-Carcinoma, Squamous Cell, pubmed-meshheading:16152579-Cell Adhesion, pubmed-meshheading:16152579-Cell Movement, pubmed-meshheading:16152579-Cell Proliferation, pubmed-meshheading:16152579-Disease Progression, pubmed-meshheading:16152579-Humans, pubmed-meshheading:16152579-Keratin-1, pubmed-meshheading:16152579-Keratins, pubmed-meshheading:16152579-Laminin, pubmed-meshheading:16152579-Male, pubmed-meshheading:16152579-Matrix Metalloproteinases, pubmed-meshheading:16152579-Mice, pubmed-meshheading:16152579-Mice, Nude, pubmed-meshheading:16152579-Neoplasm Invasiveness, pubmed-meshheading:16152579-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16152579-Phenotype, pubmed-meshheading:16152579-Prognosis, pubmed-meshheading:16152579-Skin Neoplasms, pubmed-meshheading:16152579-Tissue Culture Techniques
pubmed:year
2006
pubmed:articleTitle
Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinoma.
pubmed:affiliation
Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, School of Dental Medicine, Tufts University, Boston, MA 02111, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural