Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion

Alaa M Afify, Phillip Purnell, Laura Nguyen

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

The interaction between the transmembrane receptor CD44 on epithelial tumor cells and its ligand hyaluronan in the surrounding extracellular matrix is important in tumor progression and metastasis. CD44 is encoded by a single 20-exon gene and expressed in standard form (CD44s), as well as a myriad of CD44 variants (CD44v) generated by alternative splicing of the CD44 mRNA. Previously, we demonstrated that hyaluronan (HA) production is increased at tumor-stroma interface in invasive and metastatic human breast cancers when compared with benign or premalignant lesions. We hypothesize that CD44 expression on breast cancer cells is a major contributing factor to cell adhesion, migration and invasion. To evaluate this hypothesis we examined the effects of 3 distinct anti-CD44s and 2 anti-CD44v6 monoclonal antibodies on breast cancer cell lines that expressed high and low CD44s and CD44v6. Using these antibodies we assessed the role of CD44 in cell adhesion, cell motility, and cell invasion using immobilized HA-coated wells, wound healing assays, and modified Boyden chamber respectively. Our results showed that anti-CD44s could inhibit breast cancer cell adhesion, motility and invasion, while anti-CD44v6 inhibits cell motility. In conclusion, our data suggests that CD44s is involved in breast cancer cell adhesion, motility and invasion through interaction with HA but CD44v6 is involved only in cell motility. Furthermore we concluded that antibodies against different epitopes on CD44 mediate distinct functional effects on breast cancer cells.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalExperimental and Molecular Pathology
Volume86
Issue number2
DOIs
StatePublished - Apr 2009

Keywords

  • Breast cancer
  • CD44
  • CD44v6 adhesion
  • Motility and invasion

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

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