bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒09‒25
nine papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute
  1. The Nervous System as a Regulator of Cancer Hallmarks: Insights into Therapeutic Implications.
  2. β2-Adrenergic Receptor Signaling Pathway Stimulates the Migration and Invasion of Cancer Cells via Src Activation.
  3. [Cancer Neuroscience].
  4. The Sympathetic Nervous System Contributes to the Establishment of Pre-Metastatic Pulmonary Microenvironments.
  5. MET Oncogene Controls Invasive Growth by Coupling with NMDA Receptor.
  6. Implications of a Neuronal Receptor Family, Metabotropic Glutamate Receptors, in Cancer Development and Progression.
  7. Dose-response relationship between epidural bupivacaine dose and mortality risk after surgical resection of nonsmall-cell lung cancer.
  8. T2 Hypointense Schwannoma Masquerading As A Vascular Lesion: A Case Report.
  9. General Anesthetics in Cancer Surgery: Can Anesthesiologists Help the Patient with More than a Safe Sleep.
  1. Cancers (Basel). 2022 Sep 08. pii: 4372. [Epub ahead of print]14(18):
    The Nervous System as a Regulator of Cancer Hallmarks: Insights into Therapeutic Implications.
    Karla V Torres-Juárez, Felisbina Luisa Queiroga, Laura P Romero-Romero.
      The involvement of the nervous system in the development of cancer is controversial. Several authors have shown opinions and conflicting evidence that support the early effect of the nervous system on the carcinogenic process. For about a century, research has not been enough, questions remain open, ideas are not discarded, and although more research is still needed to answer all the questions, there is now enough evidence to support the theories and give hope of finding one more possible form of treatment. It is clear that malignant neoplasms have endogenous characteristics that allow them to establish and progress. Some of these characteristics known as hallmarks of cancer, are damage mechanisms in the pathology but necessary during other physiological processes which show some nerve dependence. The nervous system communicates with the whole organism, regulating physiological processes necessary to respond to external stimuli and for the maintenance of homeostasis. The modification of nerve activity could generate an overload and deregulate the state of cellular and tissue homeostasis; this could drive cancer development. In this review, we will address the issue in an evidence-oriented manner that supports that the nervous system is able to participate in the initial and progressive process of carcinogenesis by inducing biochemical, physiological, and cellular modifications involved in the hallmarks of cancer.
    Keywords:  cancer hallmarks; immunity neuromodulation; nervous system; neurotumoral communication; tumor innervation
    DOI:  https://doi.org/10.3390/cancers14184372
  2. Molecules. 2022 Sep 13. pii: 5940. [Epub ahead of print]27(18):
    β2-Adrenergic Receptor Signaling Pathway Stimulates the Migration and Invasion of Cancer Cells via Src Activation.
    Jae-Hoon Jeong, Hyun-Ji Park, Shin-Hyung Park, Yung-Hyun Choi, Gyoo-Yong Chi.
      Chronic stress has been reported to stimulate the release of catecholamines, including norepinephrine (NE) and epinephrine (E), which promote cancer progression by activating the adrenergic receptor (AR). Although previous studies showed that β2-AR mediated chronic stress-induced tumor growth and metastasis, the underlying mechanism has not been fully explored. In this study, we aimed to investigate the molecular mechanism by which β2-AR exerts a pro-metastatic function in hepatocarcinoma (HCC) cells and breast cancer (BC) cells. Our results showed that Hep3B human HCC cells and MDA-MB-231 human BC cells exhibited the highest ADRB2 expression among diverse HCC and BC cell lines. NE, E, and isoprenaline (ISO), adrenergic agonists commonly increased the migration and invasion of Hep3B cells and MDA-MB-231 cells. The phosphorylation level of Src was significantly increased by E/NE. Dasatinib, a Src kinase inhibitor, blocked E/NE-induced migration and invasion, indicating that AR agonists enhanced the mobility of cancer cells by activating Src. ADRB2 knockdown attenuated E/NE-induced Src phosphorylation, as well as the metastatic ability of cancer cells, suggesting the essential role of β2-AR. Taken together, our results demonstrate that chronic stress-released catecholamines promoted the migration and invasion of HCC cells and BC cells via β2-AR-mediated Src activation.
    Keywords:  Src; breast cancer; hepatocellular carcinoma; invasion; migration; β2-adrenergic receptor
    DOI:  https://doi.org/10.3390/molecules27185940
  3. Nervenarzt. 2022 Sep 21.
    [Cancer Neuroscience].
    Varun Venkataramani, Frank Winkler.
      The nervous system integrates and processes information to act as master regulator of various vital, biological processes. However, increasing data suggest that the nervous system is also a key player in the initiation of cancer and cancer progression. Following the tenet that oncology follows ontogeny, it has been shown that brain tumors follow neural developmental processes. Incurable gliomas form neurite-like membrane tubes called tumor microtubes and are controlled by neurodevelopmental pathways. Tumor microtubes are used for invasion, proliferation and interconnection with other tumor cells, forming a tumor network that is therapeutically resistant. Additionally, neurons can activate tumor cells via glutamatergic synapses to drive tumor invasion and growth. The most recent knowledge of brain cancer neuroscience presented here with a focus on brain tumours has already led to new approaches for antitumour treatment.
    Keywords:  Antitumor treatment; Brain tumors; Nervous system; Treatment resistance; Tumor network
    DOI:  https://doi.org/10.1007/s00115-022-01380-5
  4. Int J Mol Sci. 2022 Sep 13. pii: 10652. [Epub ahead of print]23(18):
    The Sympathetic Nervous System Contributes to the Establishment of Pre-Metastatic Pulmonary Microenvironments.
    Katsuaki Ieguchi, Masabumi Funakoshi, Taishi Mishima, Kohtaro Takizawa, Tsutomu Omori, Fumio Nakamura, Makoto Watanabe, Mayumi Tsuji, Yuji Kiuchi, Shinichi Kobayashi, Takuya Tsunoda, Yoshiro Maru, Satoshi Wada.
      Emerging evidence suggests that neural activity contributes to tumor initiation and its acquisition of metastatic properties. More specifically, it has been reported that the sympathetic nervous system regulates tumor angiogenesis, tumor growth, and metastasis. The function of the sympathetic nervous system in primary tumors has been gradually elucidated. However, its functions in pre-metastatic environments and/or the preparation of metastatic environments far from the primary sites are still unknown. To investigate the role of the sympathetic nervous system in pre-metastatic environments, we performed chemical sympathectomy using 6-OHDA in mice and observed a decrease in lung metastasis by attenuating the recruitment of myeloid-derived suppressor cells. Furthermore, we note that neuro-immune cell interactions could be observed in tumor-bearing mouse lungs in conjunction with the decreased expression of Sema3A. These data indicate that the sympathetic nervous system contributes to the preparation of pre-metastatic microenvironments in the lungs, which are mediated by neuro-immune cell interactions.
    Keywords:  MDSC; metastasis; metastatic niche; semaphorin; sympathetic nervous system; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms231810652
  5. Cancers (Basel). 2022 Sep 11. pii: 4408. [Epub ahead of print]14(18):
    MET Oncogene Controls Invasive Growth by Coupling with NMDA Receptor.
    Simona Gallo, Annapia Vitacolonna, Paolo Comoglio, Tiziana Crepaldi.
      The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel involved in excitatory synaptic transmission. Outside the nervous system, the NMDAR is expressed in a variety of tissues and in cancers, notably in the highly invasive and metastatic triple-negative breast carcinoma. MET encodes the tyrosine kinase receptor for HGF and is a master regulator gene for "invasive growth". In silico analysis shows that high expression of the NMDAR2B subunit is a negative prognostic factor in human invasive breast carcinoma. Here, we show that in triple-negative breast cancer cell lines NMDAR2B and MET proteins are coexpressed. HGF stimulation of these cells is followed by autophosphorylation of the MET kinase and phosphorylation of the NMDAR2B subunit at tyrosines 1252 and 1474. MET and phosphorylated NMDAR2B are physically associated, as demonstrated by co-immunoprecipitation, confocal immunofluorescence, and proximity ligation assays. Notably, pharmacological inhibition of NMDAR by MK801 and ifenprodil blunts the biological response to HGF. These results demonstrate the existence of a MET-NMDAR crosstalk driving the invasive program, paving the way for a new combinatorial therapy.
    Keywords:  MET tyrosine kinase receptor; glutamate receptor; hepatocyte growth factor; tumor invasion
    DOI:  https://doi.org/10.3390/cancers14184408
  6. Cells. 2022 Sep 13. pii: 2857. [Epub ahead of print]11(18):
    Implications of a Neuronal Receptor Family, Metabotropic Glutamate Receptors, in Cancer Development and Progression.
    Kevinn Eddy, Mohamad Naser Eddin, Anna Fateeva, Stefano Vito Boccadamo Pompili, Raj Shah, Saurav Doshi, Suzie Chen.
      Cancer is the second leading cause of death, and incidences are increasing globally. Simply defined, cancer is the uncontrolled proliferation of a cell, and depending on the tissue of origin, the cancer etiology, biology, progression, prognosis, and treatment will differ. Carcinogenesis and its progression are associated with genetic factors that can either be inherited and/or acquired and are classified as an oncogene or tumor suppressor. Many of these genetic factors converge on common signaling pathway(s), such as the MAPK and PI3K/AKT pathways. In this review, we will focus on the metabotropic glutamate receptor (mGluR) family, an upstream protein that transmits extracellular signals into the cell and has been shown to regulate many aspects of tumor development and progression. We explore the involvement of members of this receptor family in various cancers that include breast cancer, colorectal cancer, glioma, kidney cancer, melanoma, oral cancer, osteosarcoma, pancreatic cancer, prostate cancer, and T-cell cancers. Intriguingly, depending on the member, mGluRs can either be classified as oncogenes or tumor suppressors, although in general most act as an oncogene. The extensive work done to elucidate the role of mGluRs in various cancers suggests that it might be a viable strategy to therapeutically target glutamatergic signaling.
    Keywords:  MAPK; PI3K/AKT; adenylyl cyclase; cancer; glutamate; guanine nucleotide binding–protein coupled receptor; metabolism; metabotropic glutamate receptor; phospholipase C; riluzole
    DOI:  https://doi.org/10.3390/cells11182857
  7. J Chin Med Assoc. 2022 Sep 01. 85(9): 952-957
    Dose-response relationship between epidural bupivacaine dose and mortality risk after surgical resection of nonsmall-cell lung cancer.
    Hsiang-Ling Wu, Ying-Hsuan Tai, Chun-Cheng Li, Juan P Cata, Chien-Wun Wang, Kuang-Yi Chang, Mei-Yung Tsou, Shih-Pin Lin.
      BACKGROUND: Preclinical studies have shown that local anesthetics may modify the growth and invasion of cancer cells. However, few clinical studies have evaluated their impact on cancer outcomes after tumor resection.METHODS: In this single-center cohort study, patients who underwent surgical resection of stage IA through IIIB nonsmall-cell lung cancer and used patient-controlled epidural analgesia from 2005 to 2015 were recruited and followed until May 2017. Data of the epidural bupivacaine dose for each patient were obtained from infusion pump machines. Proportional hazards regression models were used to analyze the associations between bupivacaine dose with postoperative cancer recurrence and all-cause mortality.
    RESULTS: A total of 464 patients were analyzed. Among these patients, the mean bupivacaine dose was 352 mg (± standard deviation 74 mg). After adjusting for important clinical and pathological covariates, a significant dose-response relationship was observed between epidural bupivacaine dose and all-cause mortality (adjusted hazard ratio: 1.008, 95% confidence interval: 1.001-1.016, p = 0.029). The association between bupivacaine dose and cancer recurrence were not significant (adjusted hazard ratio: 1.000, 95% confidence interval: 0.997-1.002, p = 0.771). Age, sex, body mass index, mean daily maximum pain score, and pathological perineural infiltration were independently associated with bupivacaine dose.
    CONCLUSION: A dose-dependent association was found between epidural bupivacaine dose and long-term mortality among patients following surgical resection of nonsmall-cell lung cancer. Our findings do not support the hypothetical anticancer benefits of local anesthetics. More studies are needed to elucidate the role of local anesthetics in cancer treatment.
    DOI:  https://doi.org/10.1097/JCMA.0000000000000779
  8. Neurohospitalist. 2022 Oct;12(4): 659-663
    T2 Hypointense Schwannoma Masquerading As A Vascular Lesion: A Case Report.
    Zachary A Kons, Robert W Regenhardt, Adam A Dmytriw, Justin E Vranic, Anh Huynh, Matthew P Frosch, Lawrence F Borges, Aman B Patel, Javier M Romero, Christopher J Stapleton.
      Spinal schwannomas are rare nerve root tumors that typically produce subtle symptoms from nerve root compression. These tumors are known to be heterogeneously hyperintense on T2-weighted MRI and avidly enhance with contrast. However, here we describe an L5 spinal schwannoma in a 66-year-old woman that was hypointense on T2-weighted imaging with other radiographic findings more closely aligning with a vascular lesion. The neuroradiologic characteristics on MRI, time resolved MR angiography, and catheter digital subtraction angiography are presented. The patient underwent a full workup for possible dural arteriovenous fistula and thrombosed venous varix before the nerve sheath tumor was discovered intraoperatively and confirmed as a schwannoma on histopathology.
    Keywords:  nerve compression syndromes; neurooncology; spinal cord diseases
    DOI:  https://doi.org/10.1177/19418744221112539
  9. Medicina (Kaunas). 2022 Aug 25. pii: 1156. [Epub ahead of print]58(9):
    General Anesthetics in Cancer Surgery: Can Anesthesiologists Help the Patient with More than a Safe Sleep.
    John Michael Bonvini.
      Most patients suffering from neoplastic diseases will at some point during their illness be approached surgically. Surgery itself may be unfortunately responsible for tumor proliferation and metastatic spread. With the perioperative period increasingly becoming a focus of research in anesthesia, anesthesiologists have looked at the chance to influence cancer progression based on their choice of anesthesia regimen and strategy. Many anesthetic agents have been investigated for their potential impact on the course of cancer disease. There is an abundance of retrospective studies and very few prospective ones that tackled this issue. The aim of this article is to review the current state of the evidence on general anesthesia involving volatile and intravenous agents as substrates, focusing on halogenated inhalational agents and propofol, to guide clinical decision making in assessments of the best practice for perioperative management of cancer surgery.
    Keywords:  cancer surgery; general anesthetics; propofol; volatile anesthetics
    DOI:  https://doi.org/10.3390/medicina58091156
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