Ultrastructure of Human Prostate Cancer Shows Two Types of Stem Cells: Morphological Features Similar to Motile and Non-Motile Cells.

Abstract

Metastasis is responsible for about 90% of human deaths from cancer, including prostate cancer (PCa). PCa stem cell (CSC)/progenitor (putative) stem cells have localized CD 133/CD44 in fresh frozen and/or formalin-fixed, paraffin-embedded radical prostatectomy tissue sections at light microscopic levels. Our objective was to establish ultrastructural features of stem cells by transmission electron microscopy (TEM). We used paraformaldehyde and glutaraldehyde for fixation and Epon-embeding prior to making thin sections for TEM as detailed before. Electron micrographs showed two types of CSC/PS cells located near the basal portion of prostatic acini in addition to basal cells adjacent to the basal lamina. At the EM level, one type of stem cell showed numerous plasma membrane foldings at the leading edge, but not at the trailing edge, whereas the other type did not show similar modifications. For this abstract, we have designated CSC/PS cells with membrane foldings as motile-type stem cell and cells without membrane foldings as non-motile-type stem cell. In addition, motile-type stem cells had relatively elongated nuclei, peripheral and elongated mitochondria, relatively few strands of endoplasmic reticulum and some ribosomes, but essentially no secretory granules and vesicles. Non-motile-type stem cells had relatively oval nuclei, relatively few mitochondria, ribosomes and occasional granules. Both types of cells appeared as undifferentiated cells. Basal cells had ‘spindle’-shaped nuclei which were parallel to the basal lamina and cytoplasmic organelles which were similar to the non-motile-type stem cell. Acinar cell nuclei were elongated along the baso-luminal axis and the cytoplasm contained numerous secretory vesicles and granules. These cells usually reached the acinar lumen. We suggest that motile-type stem cells probably migrated from acini to prostatic stroma and beyond whereas the non-motile-type cells remained in acini as did the basal cells. Localization of CD133 by immunefluorescence and immunoperoxidase did not show two types of stem cell. This study was conducted on Institutional Review Board approved protocol and supported by the Minneapolis Veterans Affairs Medical Center. There is no conflict of interest. (poster)