The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.

Cellular prion protein (PrPC) is seminal to modulate a variety of baseline cell functions to grant homeostasis. The classic role of such a protein was defined as a chaperone-like molecule being able to rescue cell survival. Nonetheless, PrPC also represents the precursor of the deleterious misfolded variant known as scrapie prion protein (PrPSc). This variant is detrimental in a variety of prion disorders. This multi-faceted role of PrP is greatly increased by recent findings showing how PrPC in its folded conformation may foster tumor progression by acting at multiple levels. The present review focuses on such a cancer-promoting effect. The manuscript analyzes recent findings on the occurrence of PrPC in various cancers and discusses the multiple effects, which sustain cancer progression. Within this frame, the effects of PrPC on stemness and differentiation are discussed. A special emphasis is provided on the spreading of PrPC and the epigenetic effects, which are induced in neighboring cells to activate cancer-related genes. These detrimental effects are further discussed in relation to the aberrancy of its physiological and beneficial role on cell homeostasis. A specific paragraph is dedicated to the role of PrPC beyond its effects in the biology of cancer to represent a potential biomarker in the follow up of patients following surgical resection.

Ultrastructure of testicular macrophages in aging mice.

Testicular macrophages of aging mice were studied by TEM. Testicular macrophages retained with Leydig cells the close morphological relationships observed in the adult young animals, but digitations were not found. Lipofuscin granules like those of the Leydig cells from aging mice were observed in the cytoplasm. These organelles were generally absent in the testicular macrophages of young adult mice. Testicular macrophages did not display phagocytosis of the lipofuscin granules. In addition, the latter were not found in the intercellular spaces. These observations indicated that lipofuscin granules were formed, at least in a great part, within testicular macrophages as a consequence of metabolic changes occurring with age. Fine lamellar organization was seen in the lipofuscin granules of both Leydig cells and testicular macrophages. Frequently, lipofuscin granules originated from secondary lysosomes containing lipidic vacuoles only. Together with accumulation of the lipofuscin granules, changes of testicular macrophage fine morphology were observed. Endoplasmic reticulum and Golgi apparatus became poorly developed, and coated vesicles were rarely found. Fewer mitochondria were encountered, but their ultrastructure was not altered. These results suggest that in testicular macrophages lipofuscin accumulation is associated with a functional involution.

Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis.

Several studies reported that chronic alcohol consumption alters the intestinal mucosa barrier, and subsequent entrance of endotoxins into the bloodstream. In many tissues endotoxin exposure causes the expression of calprotectin (CP) and the receptor for advanced glycation -end products (RAGE). In this study we investigated whether chronic alcohol administration causes expression of CP and RAGE in mouse testis. The distribution of free and loosely bound Zn(2+) (FLB-Zn(2+)) in the testicular tissues was also evaluated. Alcohol-induced testicular damage was documented by measuring testosterone blood levels and by light and electron microscope studies. Twenty mice were treated daily for three weeks with 3.0 g/kg of a 25% solution of alcohol. Ten mice were treated in the same period of time with a solution of maltose dextrins, isocaloric to alcohol. Twenty untreated mice were used as controls. Alcohol treated mice showed diffuse expression of CP and RAGE in the interstitial cells. RAGE was found also in the basal compartment of the seminiferous tubules. Depletion of FLB-Zn(2+) was observed in the adluminal compartment of the seminiferous tubules. Expression of CP and RAGE was not found in control mice and maltose dextrin treated mice. Our results indicated novel mechanisms by which alcohol acts in testis. Indeed, CP and RAGE may cause the generation of oxidants and inflammatory mediators, with negative impact on testicular functions. Depletion of FLB-Zn(2+) may contribute to the dysregulation of spermatogenesis.

Ultrastructural and ultracytochemical study of the middle ear epithelium in the chicken, Gallus gallus domesticus.

The fine structure of the epithelium lining the tympanic cavity of the chicken was studied by TEM and SEM. In addition, the distribution of nonspecific esterase activity in the epithelium was investigated by TEM. Ultrastructural study revealed the presence of disk-like apical protrusions of the epithelial cells, previously not observed in other cell types. The protrusions contained some cytoplasmic organelles and were characterized by a ring-shaped thickening around their periphery. The ring was made up of a granulo-filamentous material. Our observations clearly indicate the existence of an apocrine secretory mechanism, consisting of a progressive detachment of disk-like protrusions from the apex of the epithelial cells. The ultracytochemical study demonstrated nonspecific esterase activity on the epithelial surface and in the secretory vesicles. We propose that nonspecific esterase is a marker for middle ear surfactant in birds.