How tumor cells make use of CD44

Area of Science:

• Developmental Biology
• Molecular Cell Biology
• Cancer Biology

Background:

• CD44, a cell surface glycoprotein, plays roles in cell adhesion and signaling.
• Specific CD44 variants, including those with exon v3, are expressed during embryonic development.
• Heparan sulfate proteoglycans are involved in growth factor binding and presentation.

Purpose of the Study:

• To investigate the function of CD44 variant v3 in limb bud development.
• To elucidate the mechanism by which CD44 interacts with FGFs and influences cell proliferation.
• To explore the potential relevance of this mechanism in cancer metastasis.

Main Methods:

• Immunohistochemical analysis of CD44v3 expression in limb buds.
• Biochemical assays to assess CD44-heparan sulfate modification.
• Functional studies using FGFs and mesenchymal cells to evaluate proliferation and outgrowth.
• Comparative analysis of CD44 variant function in developmental and cancer contexts.

Main Results:

• CD44 variant v3 is expressed in the apical ectodermal ridge of embryonic limb buds.
• This CD44 variant is modified with heparan sulfate, enabling low-affinity binding of FGFs.
• Presentation of FGFs by CD44 to mesenchymal cells stimulates cell proliferation and promotes limb outgrowth.
• A similar growth factor presentation mechanism is proposed for CD44 variants in metastasizing tumor cells.

Conclusions:

• CD44 variant v3, through heparan sulfate modification, acts as a crucial FGF receptor during embryonic limb development.
• This mechanism of growth factor presentation by CD44 is conserved and potentially contributes to tumor cell proliferation and metastasis.