Function and expression of CD44 during spreading, migration, and invasion of murine carcinoma cells

Virginia Ladeda, Julio A. Aguirre Ghiso, Elisa Bal de Kier Joffé

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


The cell surface glycoprotein CD44 is proposed as a main participant in cell adhesion and migration. We studied the function, expression, and distribution of CD44 in the invasive and metastatic F3II murine carcinoma cell line during adhesion, spreading, migration, and invasion. A mAb anti- CD44 (KM 201) dramatically blocked F3II cell adhesion on both plastic and hyal-uronic acid coatings, as well as spreading on uncoated plastic surfaces (P < 0.01). KM201 mAb significantly inhibited F3II cell migration and invasion in Transwell chambers. Immunocytochemistry of spreading cells revealed that CD44 distributed in bands on the cell surface, particularly in the tip of leading edges and in the perinuclear zones of the cell membrane. CD44 antigen was never detected in filopodia or lamellipodia nor in focal adhesion-like structures, but was also detectable as strong interlamellar bands. Fully spread cells showed a decreased CD44 signal compared to cells in early stages of spreading. This decrease correlated with a reduced expression of CD44 as detected by Western blot. We also investigated the signals that may regulate CD44 expression in F3II cells. Treatment of F3II cells, with phorbol myristate acetate (PMA) or phosphatidic acid (PA, the product of PLD- dependent hydrolysis of phosphatidylcholine), significantly enhanced CD44 expression. Conversely, the treatment of F3II cells with H7, a specific PKC inhibitor, or propranolol, which blocks PA conversion to DAG, significantly decreased CD44 expression levels. These results suggest the involvement of PKC and PLD pathways in CD44 expression. These results demonstrate that CD44 plays an important role during F3II cells adhesion, spreading, migration, and invasion. In addition we provide information linking the PLD- and PKC- dependent pathways with the regulation of CD44 expression.

Original languageEnglish
Pages (from-to)515-527
Number of pages13
JournalExperimental Cell Research
Issue number2
StatePublished - 1 Aug 1998
Externally publishedYes


  • Adhesion molecules
  • Cell motility
  • Cell signaling
  • Phorbol esters
  • Phosphatidic acid


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