Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2011

01-08-2011 | Gastrointestinal Oncology

Loss of Sympathetic Nerve Fibers Around Intratumoral Arterioles Reflects Malignant Potential of Gastric Cancer

Authors: Hideyo Miyato, MD, Joji Kitayama, MD, PhD, Hironori Ishigami, MD, Shoichi Kaisaki, MD, Hirokazu Nagawa, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2011

Login to get access

Abstract

Background

The role and clinical significance of the alteration of sympathetic nerve fibers (SNF) was assessed in gastric cancer. Loss of nerve fibers in malignant tumors has previously been described; however, how dysfunction of the nervous system is involved in cancer progression has not been clarified in clinical studies.

Materials and Methods

The distribution of SNF was examined in 82 surgically resected gastric cancer specimens with immunohistochemical staining of tyrosine hydroxylase (TH), and the association with clinicopathological findings as well as the clinical outcome of the patients was retrospectively evaluated.

Results

Arterioles in the normal gastric wall were totally covered with SNF, while the immunoreactivity to TH was markedly reduced around arterioles in cancer tissue. The degree of loss of SNF was significantly correlated with the depth of invasion (P < .0001) and lymph node metastasis (P < .0001) as well as microvessel density (MVD) (P = .0043). Moreover, patients who had tumors with marked loss of SNF showed a markedly worse clinical outcome, with an independent association by multivariate analysis.

Conclusions

Loss of periarteriolar SNF is associated with aggressive phenotype of gastric cancer possibly through enhanced angiogenesis and thus could be a useful marker to predict the clinical outcome.
Literature
1.
Willis RA. The spread of tumors in the human body. London: Butterworths, 1973;121–5.
2.
Mitchell BS, Schumacher U, Kaiserling E. Are tumours innervated? Immunohistological investigations using antibodies against the neuronal marker protein gene product 9.5 (PGP 9.5) in benign, malignant and experimental tumours. Tumour Biol. 1994;15:269–74.PubMedCrossRef
3.
Luts L, Bergenfelz A, Alumets J, Sundler F. Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas. Eur J Endocrinol. 1995;133:543–51.PubMedCrossRef
4.
Lu SH, Zhou Y, Que HP, Liu SJ. Peptidergic innervation of human esophageal and cardiac carcinoma. World J Gastroenterol. 2003;9:399–403.PubMed
5.
6.
Tallett A, Chilvers ER, MacKinnon AC, Haslett C, Sethi T. Neuropeptides stimulate tyrosine phosphorylation and tyrosine kinase activity in small cell lung cancer cell lines. Peptides. 1996;17:665–73.PubMedCrossRef
7.
Vesalius A. De Humani Corporis Fabrica. Basel: Oporinus, 1543.
8.
Mukouyama YS, Shin D, Britsch S, Taniguchi M, Anderson DJ. Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell. 2002;109:693–705.PubMedCrossRef
9.
Mukouyama YS, Gerber HP, Ferrara N, Gu C, Anderson DJ. Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin 1-mediated positive feedback. Development. 2005;132:941–52.PubMedCrossRef
10.
Kummer W, Habeck JO. Chemoreceptor A-fibres in the human carotid body contain tyrosine hydroxylase and neurofilament immunoreactivity. Neuroscience. 1992;47:713–25.PubMedCrossRef
11.
De Fontgalland D, Wattchow DA, Costa M, Brookes SJ. Immunohistochemical characterization of the innervation of human colonic mesenteric and submucosal blood vessels. Neurogastroenterol Motil. 2008;20:1212–26.PubMedCrossRef
12.
Nishizaki Y. The effects of exogenous and endogenous dopamine on the gastric microcirculation and their action sites in rat stomach. Nippon Shokakibyo Gakkai Zasshi. 1993;90:1639–51.PubMed
13.
Li ZS, Fox-Threlkeld JE, Furness JB. Innervation of intestinal arteries by axons with immunoreactivity for the vesicular acetylcholine transporter (VAChT). J Anat. 1998;192:107–17.PubMedCrossRef
14.
Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G. The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer. 1996;73:349–59.PubMedCrossRef
15.
Chamary VL, Robson T, Loizidou M, Boulos PB, Burnstock G. Progressive loss of perivascular nerves adjacent to colorectal cancer. Eur J Surg Oncol. 2000;26:588–93.PubMedCrossRef
16.
Tutton PJ, Barkla DH. The influence of adrenoceptor activity on cell proliferation in colonic crypt ipithelium and in colonic adenocarcinomata. Virchows Arch B Cell Pathol. 1977;24:139–46.PubMed
17.
Kennedy MF, Tutton PJ, Barkla DH. Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma. Br J Cancer. 1985;52:383–90.PubMedCrossRef
18.
Basu S, Nagy JA, Pal S, Vasile E, Eckelhoefer IA, Bliss VS, et al. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med. 2001;7:569–74.PubMedCrossRef
19.
Chakroborty D, Sarkar C, Basu B, Dasgupta PS, Basu S. Catecholamines regulate tumor angiogenesis. Cancer Res. 2009;69:3727–30.PubMedCrossRef
20.
Basu S, Sarkar C, Chakroborty D, Nagy J, Mitra RB, Dasgupta PS, et al. Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis. Cancer Res. 2004;64:5551–5.PubMedCrossRef
21.
Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12:939–44.PubMedCrossRef
22.
23.
Chedotal A, Kerjan G, Moreau-Fauvarque C. The brain within the tumor: new roles for axon guidance molecules in cancers. Cell Death Differ. 2005;12:1044–56.PubMedCrossRef
24.
Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res. 2006;312:584–93.PubMedCrossRef
25.
Vachkov IH, Huang X, Yamada Y, Tonchev AB, Yamashima T, Kato S, et al. Inhibition of axonal outgrowth in the tumor environment: involvement of class 3 semaphorins. Cancer Sci. 2007;98:1192–7.PubMedCrossRef
26.
Zhao XY, Chen L, Xu Q, Li YH. Expression of semaphorin 6D in gastric carcinoma and its significance. World J Gastroenterol. 2006;12:7388–90.PubMed
27.
Kim WH, Lee SH, Jung MH, Seo JH, Kim J, Kim MA, et al. Neuropilin2 expressed in gastric cancer endothelial cells increases the proliferation and migration of endothelial cells in response to VEGF. Exp Cell Res. 2009;315:2154–64.PubMedCrossRef
28.
Pan GQ, Ren HZ, Zhang SF, Wang XM, Wen JF. Expression of semaphorin 5A and its receptor plexin B3 contributes to invasion and metastasis of gastric carcinoma. World J Gastroenterol. 2009;15:2800–4.PubMedCrossRef
Metadata
Title
Loss of Sympathetic Nerve Fibers Around Intratumoral Arterioles Reflects Malignant Potential of Gastric Cancer
Authors
Hideyo Miyato, MD
Joji Kitayama, MD, PhD
Hironori Ishigami, MD
Shoichi Kaisaki, MD
Hirokazu Nagawa, MD, PhD
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1562-1

Other articles of this Issue 8/2011

Annals of Surgical Oncology 8/2011 Go to the issue

Bone and Soft Tissue Sarcomas

Retroperitoneal Sarcoma: Is It Time to Change the Surgical Policy?

Healthcare Policy and Outcomes

Preoperative Factors Predict Perioperative Morbidity and Mortality After Pancreaticoduodenectomy

Colorectal Cancer

Mucinous Rectal Cancer: Effectiveness of Preoperative Chemoradiotherapy and Prognosis

Healthcare Policy and Outcomes

Multidisciplinary Teams and Clinics: Better Care or Just More Care

Translational Research and Biomarkers

MicroRNA Expression as a Predictive Marker for Gemcitabine Response after Surgical Resection of Pancreatic Cancer

Breast Oncology

A Review of the Oncologic and Surgical Management of Breast Cancer in the Augmented Breast: Diagnostic, Surgical and Surveillance Challenges