Formation of intracellular lumina in human prostate carcinoma (DU145) cells, maturation into signet cells, and the cribriform morphology of tumors

Ultrastruct Pathol. 2016 Jul-Aug;40(4):189-99. doi: 10.3109/01913123.2016.1155684. Epub 2016 Apr 4.

Abstract

The intracellular or intracytoplasmic lumen (IL) is an enigmatic histological structure that occurs in various tumor cells. A reassessment of diverse ILs fine-structure micrographs obtained out of previous studies encompassing the human prostate carcinoma (DU145) cell line and xenotransplanted carcinomas enabled us to propose aspects of ILs development in cancer cells: a combination of altered expressions in intercellular contacts and their cytoskeletal components would favor a disarray of self-apical polarity orientation; those defects, associated with a local, entwined enriched membranous structures growing as microvilli-like formations out of a disrupted endoplasm and trans-Golgi sorting, create ILs in cells' perikarya. These misplaced intracytoplasmic domains can become enlarged through spaces made between the finger-like structures by accruing membranes of coalescent intracytoplasmic vesicles then adding microvilli and glycocalyx to constitute ILs. Cationic mucins added with or without a progressive or total loss of microvilli and content generate signet or ring cell, while ILs enlarge. Variable build-ups of these cells' populations in carcinomas result in architectural mix-up of adjacent cells around these voids, misconstrued as new lumen, and establish a "cribriform" tumor pattern that often implies a poor cancer prognosis. Alternatively, cytotoxic changes caused by anticancer pro-oxidant treatment favor membrane alterations and exaggerate the ILs in xenotransplants into intracellular crypts that accompany other tumor degenerative changes.

Keywords: Carcinoma; intracellular lumina; prostate; signet cell cribriform; ultrastructure.

MeSH terms

  • Animals
  • Carcinoma / pathology*
  • Carcinoma / ultrastructure*
  • Cell Differentiation
  • Cell Line, Tumor
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / ultrastructure*