Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-9-28
pubmed:abstractText
CD44 is a glycosylated adhesion molecule which may undergo alternative splicing of 10 possible exons to generate variant isoforms. A number of CD44 variant isoforms expressed by tumor cells have been correlated with metastatic and proliferative behavior. In this study, we have characterized CD44 isoform expression on three prostate cancer cell lines: ALVA-31, PPC-1, and LNCaP. Using reverse transcriptase-polymerase chain reaction, we have found that ALVA-31 and PPC-1 cells express multiple CD44 isoforms, including CD44s (standard form), CD44E (epithelial form), and an exon 14-containing form. In addition, two smaller forms have been detected: one using an alternative donor splice site within exon 5, and a novel form omitting exon 5 entirely. The CD44 isoforms expressed by ALVA-31 and PPC-1 cells appear to be preferentially located on the cell surface. By contrast, LNCaP cells do not express any of the CD44 forms at the RNA or protein level. Both PPC-1 and ALVA-31 cells display tumorigenesis and invasiveness in nude mice, whereas LNCap cells exhibit a less malignant phenotype, suggesting a correlation between CD44 variant (CD44v) expression and aggressive prostate tumor behavior. Functional characterization reveals that CD44 mediates prostate cell adhesion to extracellular hyaluronic acid (HA). In addition, the CD44 cytoplasmic domain binds specifically to ankyrin, a membrane cytoskeletal protein. Double immunofluorescence labeling and confocal microscopic analyses indicate that HA binding induces the HA receptor (i.e., CD44) to form capped structures. Importantly, intracellular ankyrin is preferentially accumulated underneath HA receptor-capped structures. These results suggest that cytoskeletal proteins such as ankyrin are closely associated with CD44-mediated signaling events induced by HA. Finally, HA-mediated transmembrane interactions between CD44 isoforms and cytoskeletal proteins (i.e. ankyrin) may play a pivotal role in regulating tumor cell behavior during human prostate cancer development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
605-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7544357-Ankyrins, pubmed-meshheading:7544357-Antigens, CD44, pubmed-meshheading:7544357-Base Sequence, pubmed-meshheading:7544357-Carrier Proteins, pubmed-meshheading:7544357-Cell Adhesion, pubmed-meshheading:7544357-Cytoskeleton, pubmed-meshheading:7544357-DNA Primers, pubmed-meshheading:7544357-Gene Expression Regulation, Neoplastic, pubmed-meshheading:7544357-Humans, pubmed-meshheading:7544357-Hyaluronic Acid, pubmed-meshheading:7544357-Male, pubmed-meshheading:7544357-Molecular Sequence Data, pubmed-meshheading:7544357-Prostatic Neoplasms, pubmed-meshheading:7544357-RNA, Messenger, pubmed-meshheading:7544357-RNA, Neoplasm, pubmed-meshheading:7544357-Receptors, Cell Surface, pubmed-meshheading:7544357-Receptors, Lymphocyte Homing, pubmed-meshheading:7544357-Signal Transduction, pubmed-meshheading:7544357-Tumor Cells, Cultured
pubmed:year
1995
pubmed:articleTitle
Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells.
pubmed:affiliation
Department of Cell Biology and Anatomy, University of Miami Medical School, Florida 33101, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.