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

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

Acknowledgments

This study received support through St. George’s University School of Medicine, Newcastle upon Tyne, UK and Grenada, WI, IC MedTech, El Cajon, CA and the Unité de Recherches en Physiologie Moléculaire, Laboratoire des Cellules et Tissus, Université de Namur, Belgium. Both A. Bhalla and O. Faour were junior medical students involved in scholarly activities under Dr. J. Gilloteaux while at St George’s University. Ms. Kate Adamson from Northumbria University Graphics is recognized for her assistance in producing the electronic version of the illustrations.