Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification

Abstract

The interstitial cells of Cajal (ICC) have been once negligible players, but now appear as blazing protagonists [1]. Beyond the importance for physiology and pharmacology as pace-makers [2], and for gastrointestinal pathology as the origin of GISTs [3,4], the existence of ICC raised the possibility of ICC-like cells located outside the musculature of the gastrointestinal tract [5].Indeed, during the last few years, relatively numerous articles appeared proclaiming the existence AbstractWe have previously shown the existence of ICLC in human resting mammary gland stroma by means of methylene blue (vital) staining and c-kit immunopositivity (immunofluorescence and immunohistochemistry). In addition, we reported the phenotype characteristics of these ICLC in vitro (primary cell cultures). Since the identification of ICLC outside the gut requires, at this moment, the obligatory use of TEM, we used this technique and provide unequivocal evidence for the presence of ICLC in the intralobular stroma of human resting mammary gland. According to the 'platinum standard' (10 TEM criteria for the certitude diagnosis of ICLC), we found interstitial cells with the following characteristics: 1. location: among the tubulo-alveolar structures, in the non-epithelial space; 2. caveolae: ~2.5% of cell volume; 3. mitochondria: ~10% of cell volume; 4. endoplasmic reticulum: either smooth or rough, ~2-3% of cell volume; 5. cytoskeleton: intermediate and thin filaments, as well as microtubules are present; 6. myosin thick filaments: undetectable; 7. basal lamina: occasionally found; 8. gap junctions: occasionally found; 9. close contacts with targets: nerve fibers, capillaries, immunoreactive cells by 'stromal synapses'; 10. characteristic cytoplasmic processes: i) number: frequently 2-3; ii) length: several tens of μm; iii) thickness: uneven caliber, 0.1-0.5 μm, with dilations, but very thin from the emerging point; iv) aspect: moniliform, usually with mitochondria located in dilations; v) branching: dichotomous pattern; vi) Ca 2+ release units: are present; vii) network labyrinthic system: overlapping cytoplasmic processes. It remains to be established which of the possible roles that we previously suggested for ICLC (e.g. juxta-and/or paracrine secretion, uncommited progenitor cells, immunological surveillance, intercellular signaling, etc.) are essential for the epithelium/stroma equilibrium in the mammary gland under normal or pathological conditions.

Interstitial Cajal‐like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization

“…A B [12]; female [13][14][15] or male [16,17] reproductive tract; upper [18] or lower [19][20][21] urinary tract; mammary gland [22], etc. Moreover, besides the well-known gastrointestinal stromal tumors (socalled GISTs), which start from ICC, extra-GISTs are now considered a new pathological entity, originating probably from ICLC [23].…”

Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?

“…The possibility that the TC could be a variant of the ICC outside the gut was taken into consideration since these cells were described and for this reason these cells were initially named interstitial ICLC (46). This name, however, soon showed its ambiguity and vagueness and the term TC, considered more identifiably, was proposed (1).…”

A comprehensive guide to telocytes and their great potential in cardiovascular system

“…They initially called them Interstitial Cajal-like Cells (ICLC) (3). After that discovery Pieri et al re-examined the muscular coat of the gut only to fi nd out that ICLC are present there in great quantities, coexisting with the ICC and often share an identical distribution (4).…”