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Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms

S B Fox1, J Fawcett, D G Jackson

  • 1Nuffield Department of Pathology, University of Oxford, United Kingdom.

Cancer Research
|August 15, 1994
PubMed
Summary

The CD44 receptor, crucial for cell adhesion, exhibits diverse protein variants (vCD44) due to alternative splicing. This study found that vCD44 expression varies significantly in tumors and normal tissues, challenging its proposed role in metastasis.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • The CD44 receptor, a lymphocyte-homing and hyaluronan receptor, exists in over 20 isoforms generated by alternative splicing of exons v1-v10.
  • Previous studies, primarily at the mRNA level, suggested tissue-specific CD44 variant expression, but protein-level analysis was limited by antibody availability.
  • Recent reports of exon-specific antibodies detecting vCD44 variants, particularly those including the v6 exon, in human tumors have linked them to metastasis.

Purpose of the Study:

  • To investigate the protein-level expression of various CD44 splice variants (vCD44) across a wide range of normal and neoplastic human tissues.
  • To assess the role of specific vCD44 isoforms, including those with the v6 exon, in tumor progression and metastasis.
  • To provide a comprehensive analysis of vCD44 expression patterns using a novel panel of monoclonal antibodies.

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Main Methods:

  • Generation of a comprehensive panel of CD44 exon-specific monoclonal antibodies against a recombinant CD44(v3-10)-immunoglobulin chimera.
  • Analysis of vCD44 expression at the protein level in a large cohort of normal and cancerous human tissues.
  • Utilizing exon-specific antibodies to identify the presence and levels of specific vCD44 isoforms, including those containing v3, v4/5, v6, and v8/9 exons.

Main Results:

  • vCD44 expression demonstrated significant variability among different human tumors, with some exhibiting minimal or no vCD44.
  • Expression was not confined to isoforms containing the v6 exon; variants including v3, v4/5, and v8/9 were also detected.
  • Normal epithelial tissues showed considerable expression of the same vCD44 isoforms found in tumors.

Conclusions:

  • The widespread expression of vCD44 isoforms, including those beyond v6, in normal tissues contradicts a universally causative role in tumor metastasis.
  • The significant variation in vCD44 expression across tumor types suggests context-dependent functions rather than a general role in promoting tumor growth.
  • Further research is needed to elucidate the specific functions of different vCD44 isoforms in normal physiology and various disease states.