Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

We describe here ‐ presumably for the first time‐a Cajal‐like type of tubal interstitial cells (t‐ICC), resembling the archetypal enteric ICC. t‐ICC were demonstrated in situ and in vitro on fresh preparations (tissue cryosections and primary cell cultures) using methylene‐blue, crystal‐violet, Janus‐Green B or Mito Tracker‐Green FM Probe vital stainings. Also, t‐ICC were identified in fixed specimens by light microscopy (methylene‐blue, Giemsa, trichrome stainings, Gomori silver‐impregnation) or transmission electron microscopy (TEM). The positive diagnosis of t‐ICC was strengthened by immunohistochemistry (IHC; CD117/c‐kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c‐kit+ and other 7 antigens). The spatial density of t‐ICC (ampullar‐segment cryosections) was 100–150 cells/mm2. Non‐conventional light microscopy (NCLM) of Epon semithin‐sections revealed a network‐like distribution of t‐ICC in lammina propria and smooth muscle meshwork. t‐ICC appeared located beneath of epithelium, in a 10–15μ thick ‘belt’, where 18±2% of cells were t‐ICC. In the whole lamina propria, t‐ICC were about 9%, and in muscularis ∼7%. In toto, t‐ICC represent ∼8% of subepithelial cells, as counted by NCLM. In vitro, t‐ICC were 9.9±0.9% of total cell population. TEM showed that the diagnostic ‘gold standard’ (Huizinga et al., 1997) is fulfilled by ‘our’ t‐ICC. However, we suggest a ‘platinum standard’, adding a new defining criterion ‐ characteristic cytoplasmic processes (number: 1–5; length: tens of μm; thickness: ±0.5μ; aspect: moniliform; braching: dichotomous; organization: network, labyrinthic‐system). Quantitatively, the ultrastructural architecture of t‐ICC is: nucleus, 23.6±3.2% of cell volume, with heterochromatin 49.1±3.8%; mitochondria, 4.8±1.7%; rough and smooth endoplasmic‐reticulum (1.1±0.6%, 1.0±0.2%, respectively); caveolae, 3.4±0.5%. We found more caveolae on the surface of cell processes versus cell body, as confirmed by IF for caveolins. Occasionally, the so‐called ‘Ca2+‐release units’ (subplasmalemmal close associations of caveolae+endoplasmic reticulum±mitochondria) were detected in the dilations of cell processes. Electrophysiological single unit recordings of t‐ICC in primary cultures indicated sustained spontaneous electrical activity (amplitude of field potentials: 57.26±6.56mV). Besides the CD117/c‐kit marker, t‐ICC expressed variously CD34, caveolins 1&2, α‐SMA, S‐100, vimentin, nestin, desmin, NK‐1. t‐ICC were negative for: CD68, CD1a, CD62P, NSE, GFAP, chromogranin‐A, PGP9.5, but IHC showed the possible existence of (neuro)endocrine cells in tubal interstitium. We call them ‘JF cells’. In conclusion, the identification of t‐ICC might open the door for understanding some tubal functions, e.g. pace‐making/peristaltism, secretion (auto‐, juxta‐ and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and intercellular signaling, via the very long processes. Furthermore, t‐ICC might even be uncommitted bipotential progenitor cells.

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“…Nestin tumors and intestinal cells of Cajal [82]. Some of t-ICC in our experiment expressed nestin (Fig.…”

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confidence: 50%

Novel type of interstitial cell (Cajal-like) in human fallopian tube

et al. 2005

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“…Conversely, epithelioid cells are arranged in organoid clusters or sheets. Approximately 90% of GISTs are immunohistochemically positive for KIT, and muta- tions of the KIT gene have been found in most of these KIT-positive GISTs [1][2][3][4][5][6] . PDGFRA gene mutations have been reported in some GISTs in the absence of KIT gene mutations [7,8] .…”

Section: Differential Diagnosismentioning

confidence: 99%

“…The majority of gastrointestinal mesenchymal tumors are gastrointestinal stromal tumors (GISTs) that are characterized by a high frequency of positive immunohistochemical reactivity for KIT and mutations of the KIT gene [1][2][3][4][5][6] . Mutations of the platelet-derived growth factor receptor α (PDGFRA) gene have been reported in GISTs that are negative for mutations in KIT [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach

Takahashi

Shimizu

Ishida

et al. 2007

American Journal of Surgical Pathology

102

131

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Plexiform angiomyxoid myofibroblastic tumor of the stomach is a unique mesenchymal tumor that we first described in 2007. The tumor is very rare, and to date, only 18 cases confirmed by immunohistochemistry have been reported in the literature. The patients' ages ranged from 7 to 75 years (mean, 43 years), and the male-to-female ratio was approximately 1:1. Representative clinical symptoms are ulceration, associated upper gastrointestinal bleeding (hematemesis), and anemia. The tumors are located at the antrum in all cases, and grossly, the tumor is whitish to brownish or reddish, and forms a lobulated submucosal or transmural mass. Microscopically, the tumor is characterized by a plexiform growth pattern, the proliferation of cytologically bland spindle cells, and a myxoid stroma that is rich in small vessels and positive for Alcian blue stain. Immunohistochemically, the tumor cells are positive for α-smooth muscle actin and negative for KIT and CD34. Differential diagnoses include gastrointestinal stromal tumor and other mesenchymal tumors of the gastrointestinal tract. Some authors proposed that this tumor should be designated as "plexiform fibromyxoma", but this designation might cause confusion. The tumor is probably benign and thus far, neither recurrence nor metastasis has been reported.

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“…18,19,40) Previous observation suggested that testis Nestin + cells also express GATA-4 that involved in embryogenesis and myocardial differentiation and function maintenance. 16,41) Similar to other organs, we have found that Nestin also exists in the myocardium and up-regulates early in DCM mice, which might be associated with inhibiting cardiomyocyte depletion.…”

Section: Discussionmentioning

confidence: 99%

“…13,14) Except for neural stem cells, Nestin also have been reported to be expressed in many other tissues, such as the bone marrow, kidney, testis, and hair follicle of the skin, which participate in cell renewal, proliferation, differentiation, and tissue regeneration as well as repair. [15][16][17][18][19] Importantly, previous studies have reported that Nestin was up-regulated in the infarcted myocardium within 48 hours, and further indicated that Nestin + cells participate in the wound healing NESTIN + CELLS ENHANCE SURVIVAL OF DOXORUBICIN INDUCED HL-1 CELLS after myocardial injury. 20,21) However, whether Nestin + cells participated in the pathogenesis of the DCM has not been reported yet.…”

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confidence: 90%

Cardiac Nestin<sup>+</sup> Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells

Xie

Liao

et al. 2018

Int. Heart J.

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SummaryDilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a special marker of stem/progenitor cells in various tissues, and the tissue resident Nestin + cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin + cells participate in the protection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocardiography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin + cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels after day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin + cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin + cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin + cells might be an etiology to DCM pathogenesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.(Int Heart J 2018; 59: 180-189)

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Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

Cited by 81 publications

References 36 publications

Novel type of interstitial cell (Cajal-like) in human fallopian tube

Novel type of interstitial cell (Cajal-like) in human fallopian tube

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach

Cardiac Nestin<sup>+</sup> Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells

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