Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer

Prostate. 2009 May 15;69(7):787-98. doi: 10.1002/pros.20928.


Background: Hormonal therapy is effective for advanced prostate cancer (PC) but the disease often recurs and becomes hormone-refractory. It is hypothesized that a subpopulation of cancer cells, that is, cancer stem cells (CSCs), survives hormonal therapy and leads to tumor recurrence. CD44 expression was shown to identify tumor cells with CSC features. PC contains secretory type epithelial cells and a minor population of neuroendocrine cells. Neuroendocrine cells do not express androgen receptor and are quiescent, features associated with CSCs. The purpose of the study was to determine the expression of CD44 in human PC and its relationship to neuroendocrine tumor cells.

Methods: Immunohistochemistry and immunofluorescence were performed to study CD44 expression in PC cell lines, single cells from fresh PC tissue and archival tissue sections of PC. We then determined if CD44+ cells represent neuroendocrine tumor cells.

Results: In human PC cell lines, expression of CD44 is associated with cells of NE phenotype. In human PC tissues, NE tumor cells are virtually all positive for CD44 and CD44+ cells, excluding lymphocytes, are all NE tumor cells.

Conclusions: Selective expression of the stem cell-associated marker CD44 in NE tumor cells of PC, in combination with their other known features, further supports the significance of such cells in therapy resistance and tumor recurrence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Chromogranin A / biosynthesis
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Hyaluronan Receptors / biosynthesis*
  • Immunohistochemistry
  • Male
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / immunology*
  • Neuroendocrine Tumors / immunology*
  • Neuroendocrine Tumors / pathology
  • Phosphopyruvate Hydratase / biosynthesis
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction


  • CD44 protein, human
  • Chromogranin A
  • Hyaluronan Receptors
  • Phosphopyruvate Hydratase