An &lt;em&gt;In Vivo&lt;/em&gt; Murine Sciatic Nerve Model of Perineural Invasion

Deborde, Sylvie; Yu, Yasong; Marcadis, Andrea; Chen, Chun‐Hao; Fan, Ning; Bakst, Richard L.; Wong, Richard J.

doi:10.3791/56857

Cited by 15 publications

(21 citation statements)

References 15 publications

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“…Notably, the effects of PNI can be analyzed by monitoring hind limb motor performance, such as the hind paw width of the mice, as well as sciatic neurological score. More importantly, this model, with the genetic manipulation of mice and/or use of different types of cancer cells, can be applied to study cellular and molecular mechanisms involved in PNI and the effects of therapeutic agents on neural invasion (78). These emerging models of PNI strongly suggested there is an extensive signaling interaction between the nerves and invading tumor cells.…”

Section: Pni Modelsmentioning

confidence: 99%

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

et al. 2020

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Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are prone to perineural invasion (PNI) of the head and neck. The prognosis of patients with SACC is strongly associated with the presence of perineural spread (PNS). Although many contributing factors have been reported, the mechanisms underlying the preferential destruction of the blood-nerve barrier (BNB) by tumors and the infiltration of the tumor microenvironment by nerve fibers in SACC, have received little research attention. This review summarizes the current knowledge concerning the characteristics of SACC in relation to the PNI, and then highlights the interplay between components of the tumor microenvironment and perineural niche, as well as their contributions to the PNI. Finally, we provide new insights into the possible mechanisms underlying the pathogenesis of PNI, with particular emphasis on the role of extracellular vesicles that may serve as an attractive entry point in future studies.

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Section: Pni Modelsmentioning

confidence: 99%

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

et al. 2020

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“…Most of the observations on PNI were made using a currently limited number of in vitro and in vivo models (Amit et al, 2016;Deborde et al, 2018;Demir et al, 2012a;Liebig et al, 2009), and very few large-scale studies of PNI tissues have been performed until now: Gene expression of microdissected PNI and non-PNI salivary adenoid cystic carcinoma cells (Chen et al, 2007), and gene and microRNA profiles were analyzed in bulk prostate cancer tissues from cases with or without PNI (Prueitt et al, 2008). In the pancreas, transcriptome and proteome of high and low nerveinvasive PDAC cell lines injected in NOD/SCID (nonobese diabetes/severe combined immunodeficient) mice were described (Abiatari et al, 2009;Hibi et al, 2009;Koide et al, 2006), but no large-scale molecular data from cancer cells or nerves within PNI tissues are available as yet.…”

Section: Introductionmentioning

confidence: 99%

Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling

et al. 2019

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Perineural invasion ( PNI ) is a common and characteristic feature of pancreatic ductal adenocarcinoma ( PDAC ) that is associated with poor prognosis, tumor recurrence, and generation of pain. However, the molecular alterations in cancer cells and nerves within PNI have not previously been comprehensively analyzed. Here, we describe our proteomic analysis of the molecular changes underlying neuro‐epithelial interactions in PNI using liquid chromatography–mass spectrometry ( LC ‐ MS / MS ) in microdissected PNI and non‐ PNI cancer, as well as in invaded and noninvaded nerves from formalin‐fixed, paraffin‐embedded PDAC tissues. In addition, an in vitro model of PNI was developed using a co‐culture system comprising PDAC cell lines and PC 12 cells as the neuronal element. The overall proteomic profiles of PNI and non‐ PNI cancer appeared largely similar. In contrast, upon invasion by cancer cells, nerves demonstrated widespread plasticity with a pattern consistent with neuronal injury. The up‐regulation of SCG 2 (secretogranin II ) and neurosecretory protein VGF (nonacronymic) in invaded nerves in PDAC tissues was further validated using immunohistochemistry. The tested PDAC cell lines were found to be able to induce neuronal plasticity in PC 12 cells in our in vitro established co‐culture model. Changes in expression levels of VGF , as well as of two additional proteins previously reported to be overexpressed in PNI , Nestin and Neuromodulin ( GAP 43), closely recapitulated our proteomic findings in PDAC tissues. Furthermore, induction of VGF , while not necessary for PC 12 survival, mediated neurite extension induced by PDAC cell lines. In summary, here we report the proteomic alterations underlying PNI in PDAC and confirm that PDAC cells are able to induce neuronal plasticity. In addition, we describe a novel, simple, and easily adaptable co‐culture model for in vitro study of neuro‐epithelial interactions.

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“…7 d). To examine the effect of Schwann cell activation on cancer pain in vivo, we used a sciatic nerve perineural invasion (PNI) model that is known to induce Schwann cell activation 13 , 40 , 41 . We used sham mice that received only the incision but no cancer implantation as a control.…”

Section: Resultsmentioning

confidence: 99%

TNFα promotes oral cancer growth, pain, and Schwann cell activation

Salvo

Scheff

et al. 2021

Sci Rep

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Oral cancer is very painful and impairs a patient’s ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNFα activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNFα is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNFα reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNFα alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNFα. Cancer- or TNFα-activated Schwann cells release pro-nociceptive mediators such as TNFα and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNFα. Our study suggests that TNFα promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNFα or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.

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An <em>In Vivo</em> Murine Sciatic Nerve Model of Perineural Invasion

Cited by 15 publications

References 15 publications

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling

TNFα promotes oral cancer growth, pain, and Schwann cell activation

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