Cajal-type cells from human mammary gland stroma: phenotype characteristics in cell culture

Radu, Eugen; Regalia, T.; Ceafalan, Laura Cristina; Andrei, Florin; Crețoiu, Dragoș; Popescu, Laurențiu M.

doi:10.1111/j.1582-4934.2005.tb00509.x

Cited by 40 publications

(29 citation statements)

References 19 publications

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“…Also, we described the phenotype characteristics of mammary ICLC in primary cell cultures [19]. However, the unequivocal identification of ICLC outside the gut requires, for the time being, the obligatory use of TEM [5].…”

Section: Introductionmentioning

confidence: 99%

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

2005

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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.

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Section: Introductionmentioning

confidence: 99%

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

2005

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“…Using methylene blue dye or heavy metal impregnation techniques, he demonstrated that interstitial cells stained differently from nerve cells with which they kept a close spatial relationship. Nowadays, these interstitial cells were found in a wide variety of organs [3] including pancreas [4], urinary tract [5][6][7], uterus [8,9], fallopian tube [10], mammary gland [11,12], heart [13][14][15], blood vessel wall [16,17] and, indeed, gastrointestinal tract [18].…”

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Interstitial Cells of Cajal (ICC) and Gastrointestinal Stromal Tumor (GIST): facts, speculations, and myths

Min

Leabu

2006

Journal of Cellular and Molecular Medicine

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Interstitial cells of Cajal (ICC) is a peculiar cell network composed of cells having processes described by the eminent Spanish neuroanatomist of the 19 th century, S. Ramon y Cajal. ICC became a fascinating subject to many investigators and it is estimated that there are over 100 publications yearly on the subject related to ICC, in the last three years. Now it is widely accepted that ICC are pace maker cells of the gut and probable progenitor cells of gastrointestinal stromal tumors (GIST). Lately, interstitial Cajal-like cells (ICLC) are being found in various organs and their physiological role is still to be defined. We have reviewed the literature trying to evaluate the validity of the current concept and found that there are a few salient points to be considered. 1) There has been some important departure in defining the identity of ICC from the original criteria of Cajal. In particular, ICC with myoid feafures in intestinal smooth muscle layers (ICC-DPM) do not seem to fit to the original description of interstitial cell network by Cajal. We have also pointed out that the current reports assigning a pace maker role to ICC vastly depend on the scientific data on "ICC with myoid features", not on "fibroblast-like ICC", which are more abundant and easier to identify. 2) There seem to be an overwhelming amount of data proving the relationship between ICC and GIST. Both are known to express c-Kit and the ultrastructural characteristics seen in GIST roughly parallel those of ICC including minimal myoid differentiation seen in the majority of GIST, supporting the current concept that GIST are ICC tumors. 3) According to the original description of Cajal, ICC was not limited to the gut, suggesting an existence of ICC in other organs. The list of organs reported to contain ICC (currently identified by immunohistochemistry and electron microscopy) is ever growing and further studies are needed to define their identity and pathophysiologic role. 4). Recent data concerning gut development suggest that both c-Kit expressing ICC (fibroblasts-like as well as muscle-like) and gut muscle cells Their physiologic role was not clear at that time and even today, but Cajal speculated on a possible ancillary neural function, because of their anatomic proximity and morphologic similarity to nerves. In fact, interstitial cells of the gut are neither neural nor muscular, but are interposed between nerve and muscle cells. He considered that they might play a controlling function of the gut motility, and he thereby stimulated many investigators to study his concept. Consequently, a vast amount of data has been accumulated on 1) their existence, 2) the ultrastructural characterization of a possible pacemaker role in the gut, 3) electrophysiologic studies of peristalsis, 4) c-Kit as a molecular marker of ICC, and 5) as progenitor cells of gastrointestinal stromal tumors (GIST). The data thus far accumulated is vast and complex, but has promulgated the definition and identification of ICC [19].In recent years, much interesti...

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“…Giemsa stains previously identified ICLCs in the mammary gland stroma (Radu et al, 2005) and the fallopian tube (Popescu et al, 2005a). According to our findings, this stain is also reliable in identifying the PICCs/ portal telocytes, before any immunohistochemical labeling.…”

Section: Discussionmentioning

confidence: 68%

Extrahepatic and Intrahepatic Human Portal Interstitial Cajal Cells

Rusu

Pop

Hostiuc³

et al. 2011

The Anatomical Record

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Portal interstitial cells of Cajal (PICCs), acting as vascular pacemakers, were previously only identified in nonhumans. Moreover, there is no evidence available about the presence of such cells within the liver. The objective of the study is to evaluate whether or not PICCs are identifiable in humans and, if they are, whether or not they are following the scaffold of portal vein (PV) branches within the liver. We obtained extrahepatic PVs and liver samples from six adult human cadavers, negative for liver disease, in accordance with ethical rules. They were stained with hematoxylin-eosin (HE) and Giemsa, and then we performed immunohistochemistry on formalin-fixed paraffin-embedded specimens for CD117/c-kit, a marker of the Cajal's cells. Immune labeling was also performed for S-100 protein, desmin, glial fibrillary acidic protein (GFAP), neurofilaments, a-smooth muscle actin (a-SMA), and CD34. c-kit-Positive PICCs were identified within the extrahepatic PV, in portal spaces, and septa. On adjacent sections, these PICCs were negative for all the other antibodies used. In conclusion, our study confirms the presence of extrahepatic PICCs on humans, which may act as a possible intrinsic pacemaker in the human PV. However, the intrahepatic PICCs, which were evidenced here for the first time, are in need for further experimental studies to evaluate their functional role. A promising further direction of the study is the PICCs role in the idiopathic portal hypertension. Anat Rec, 294:1382Rec, 294: -1392Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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Cajal-type cells from human mammary gland stroma: phenotype characteristics in cell culture

Cited by 40 publications

References 19 publications

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

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

Interstitial Cells of Cajal (ICC) and Gastrointestinal Stromal Tumor (GIST): facts, speculations, and myths

Extrahepatic and Intrahepatic Human Portal Interstitial Cajal Cells

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