Platelet‐derived growth factor receptor‐α cells in mouse urinary bladder: a new class of interstitial cells

Koh, Byoung H.; Roy, Rishiparna; Hollywood, Mark A.; Thornbury, Keith D.; McHale, Noel G.; Sergeant, Gerard P.; Hatton, William J.; Ward, Sean M.; Sanders, Kenton M.; Koh, Sang Don

doi:10.1111/j.1582-4934.2011.01506.x

Cited by 85 publications

(97 citation statements)

References 45 publications

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“…at 1-2 d of age (P2). More detailed information including the protocols for assessing spinal inflammation can be found in SI Methods (23,26,(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81). …”

Section: Methodsmentioning

confidence: 99%

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Saloman

Albers

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

280

243

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro-and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.sensory neuron | pancreatic ductal adenocarcinoma | tumorigenesis | inflammation | PanIN P ancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a median survival of ∼6 mo from diagnosis (National Cancer Institute). A number of unique features distinguish PDAC from other carcinomas, but the most striking is the exuberant desmoplastic infiltrate within tumors. This compartment exhibits an array of cell types, including activated myofibroblasts and myeloid-derived cells. Indeed, this inflammatory infiltrate is present at the inception of neoplasia and accumulates at a near exponential rate during progression to carcinoma and tumor formation. It provides a complex balance of pro-and antitumorigenic signals to neoplastic cells (and also to each other) that is a focus of intense investigation. The pancreas tumor microenvironment has been studied previously, but new tools [genetically engineered mouse models (GEMs) that faithfully recapitulate the salient features of human PDAC] now allow for a careful dissection of the stroma. Using these models, we showed that generalized inflammation is required for the development of precancerous pancreatic intraepithelial neoplasias (1) and that Hedgehog-dependent stromal elements, including activated myofibroblasts, serve to constrain tumor growth and spread (2). Other cellular components of the pancreatic inflammatory str...

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“…at 1-2 d of age (P2). More detailed information including the protocols for assessing spinal inflammation can be found in SI Methods (23,26,(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81). …”

Section: Methodsmentioning

confidence: 99%

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Saloman

Albers

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

280

243

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“…Fundus muscularis tunica was fixed, prepared and visualized as reported previously. 21 Briefly, tissues were incubated overnight with a goat polyclonal antibody raised against c-kit (ACK2, 1:500 dilution in PBS; R&D Systems, MN, USA). Immunoreactivity was detected using Alexa-488 labeled donkey anti-goat IgG (1:500 in PBS; Molecular Probes/Invitrogen, NY, USA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Responses to Enteric Motor Neurons in the Gastric Fundus of Mice With Reduced Intramuscular Interstitial Cells of Cajal

Sanders

Salter

Hennig

et al. 2014

J Neurogastroenterol Motil

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Background/AimsInterstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pacemakers is well established, however their participation in neurotransmission is controversial. Studies using mutant animals that lack ICC have yielded variable conclusions on their importance in enteric motor responses. The purpose of this study was to:(1) clarify the role of intramuscular ICC (ICC-IM) in gastric motor-neurotransmission and (2) ConclusionsThis study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plasticity changes in neuronal responses that may explain discrepancies in previous functional studies which utilized mutant animals to examine the role of ICC-IM in gastric enteric motor responses.

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“…TCs may be nurse cells, integrating local, short-distance signals (direct contacts, exosomes and shedding vesicles) and long-distance signals through the long TPs, due to their 3D network. Recent studies have demonstrated a particular immunophenotype (34,35), distinct microRNA expression (36), specific gene-expression profiles (37) and peculiar electrophysiological properties of TCs in various organs (38). Close contact between TCs and fibroblasts was indicated in the present study.…”

Section: Discussionmentioning

confidence: 53%

Ultrastructural identification of telocytes in the muscularis of chicken ileum

Yang

Liu

Ahmed

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Telocytes (TCs) are a specialized type of interstitial cells, characterized by a small cell body and long, thin processes, that have recently been identified in various cavitary and non-cavitary organs of humans and laboratory mammals. Chickens present significant economical and scientific notability; however, ultrastructural identification of TCs remains unclear in birds. The aim of the present study was to describe electron microscopic evidence for the presence of TCs in the chicken gut. The ileum of healthy adult broiler chickens (n=10) was studied by transmission electron microscopy. TCs are characterized by several, long (tens to hundreds of µm) prolongations called telopodes (Tps). Tps, which are below the resolving power of light microscopy, display podomeres (thin segments of ≤0.2 µm) and podoms (dilations accommodating caveolae, mitochondria and endoplasmic reticulum). TCs were observed in every field, but were predominantly located in the myenteric plexus and the lamina propria. Tps frequently establish close spatial relationships with immune cells, blood vessels and nerve endings. On the basis of their distribution and morphology, it was hypothesized that the different locations of TCs may be associated with different roles.

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Platelet‐derived growth factor receptor‐α cells in mouse urinary bladder: a new class of interstitial cells

Cited by 85 publications

References 45 publications

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Responses to Enteric Motor Neurons in the Gastric Fundus of Mice With Reduced Intramuscular Interstitial Cells of Cajal

Ultrastructural identification of telocytes in the muscularis of chicken ileum

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