Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells

Catherine Welsh, Dan Zhu, Lilly Y W Bourguignon

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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 cytoskeleta[ 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.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalJournal of Cellular Physiology
Volume164
Issue number3
DOIs
StatePublished - Sep 1 1995

Fingerprint

Hyaluronic Acid
Cytoskeleton
Ankyrins
Prostatic Neoplasms
Protein Isoforms
Cells
Exons
Tumors
Cytoskeletal Proteins
Prostate
RNA Splice Sites
Polymerase chain reaction
RNA-Directed DNA Polymerase
Cell adhesion
Alternative Splicing
Neoplasms
Labeling
Membrane Proteins
Adhesion
Reverse Transcriptase Polymerase Chain Reaction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells. / Welsh, Catherine; Zhu, Dan; Bourguignon, Lilly Y W.

In: Journal of Cellular Physiology, Vol. 164, No. 3, 01.09.1995, p. 605-612.

Research output: Contribution to journalArticle

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