Nerve fibers in tumors of the human urinary bladder

Seifert, Péter; Bénédic, Michaël; Effert, Peter J.

doi:10.1007/s004280100496

Cited by 43 publications

(24 citation statements)

References 38 publications

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“…This indicates that cancer-related neurogenesis does occur in breast cancer, which is similar to previously reported observation that active neurogenesis occur in prostate cancer [4], colorectal cancer [5], esophageal and cardiac carcinoma [11], tumors of the human urinary bladder [12] and choroidal melanoma [13]. Taken together, this novel phenomenon that cancer initiates its own innervations may be universal.…”

Section: Discussionsupporting

confidence: 87%

The clinicopathological significance of neurogenesis in breast cancer

et al. 2014

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BackgroundRecent reports support a novel biological phenomenon about cancer related neurogenesis. However, little is known about the clinicopathological significance of neurogenesis in breast cancer.MethodsA total of 196 cases, including 20 of normal tissue, 14 of fibroadenoma, 18 of ductal carcinoma in situ (DCIS) and 144 of invasive ductal carcinoma (IDC) of the breast were used. The tissue slides were immunostained for protein gene product (PGP) 9.5 and S 100 to identify nerves. The correlation between the expression of PGP 9.5 and clinicopathological characteristics in IDC of the breast was assessed.ResultsWhile the PGP 9.5 positive nerve fibers are identified in all cases of normal breast tissue controls and in the tumor stroma of 61% (89/144) cases of invasive ductal carcinomas, PGP 9.5 positive nerve fibers are not seen in the tumor stroma of cases of fibroadenoma and DCIS. The percentage of tumors that exhibited neurogenesis increased from tumor grade I to tumor grade II and III (29.4% vs 71.8%, p < 0.0001). In addition, patients with less than 3 years of disease-free survival tended to have a higher positive expression of PGP 9.5 compared to patients with an equal or more than 3 years of disease-free survival (64.8% vs 46.7%, p = 0.035). Furthermore, moderate/strong expression of PGP 9.5 was found to be significantly related to microvessel density (MVD, p = 0.014). Interestingly, PGP 9.5 expression was significantly associated with higher MVD in the ER-negative (p = 0.045) and node-negative (p = 0.039) subgroups of IDC of the breast.ConclusionsThis data indicates that neurogenesis is associated with some aggressive features of IDC including tumor grade and patient survival as well as angiogenesis, especially in ER-negative and node-negative subtypes of IDC of the breast. Thus, neurogenesis appears to be associated with breast cancer progression and may play a role in therapeutic guidance for patients with ER-negative and node-negative invasive breast cancer.

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Section: Discussionsupporting

confidence: 87%

The clinicopathological significance of neurogenesis in breast cancer

et al. 2014

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“…Under a transmission electron microscope, a small number of fine unmyelinated nerve fibers were found containing clear and dense core vesicles in tumors. Recently, they examined the exophytic tumors of the urinary bladder and human choroidal melanoma [24,25] , and also found irregularly distributed fine nerve strands comprised of axons; hence they concluded that tumors may be innervated. In this regard, they happened to have the same view with us.…”

Section: Discussionmentioning

confidence: 99%

Peptidergic innervation of human esophageal and cardiac carcinoma

Zhou²,

Que³

et al. 2003

WJG

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AIM:To investigate the distribution of neuropeptideimmunoreactive nerve fibers in esophageal and cardiac carcinoma as well as their relationship with tumor cells so as to explore if there is nerve innervation in esophageal and cardiac carcinoma. METHODS:Esophageal and cardiac carcinoma specimens were collected from surgical operation. One part of them were fixed immediately with 4 % paraformaldehyde and then cut with a cryostat into 40-µm-thick sections to perform immunohistochemical analysis. Antibodies of ten kinds of neuropeptide including calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP), etc. were used for immunostaining of nerve fibers. The other part of the tumor specimens were cut into little blocks (1 mm 3 ) and cocultured with chick embryo dorsal root ganglia (DRG) to investigate if the tumor blocks could induce the neurons of DRG to extend processes, so as to probe into the possible reasons for the nerve fibers growing into tumors. RESULTS:Substantial amounts of neuropeptide including GAL-, NPY-, SP-immunoreactive nerve bundles and scattered nerve fibers were distributed in esophageal and cardiac carcinomas. The scattered nerve fibers waved their way among tumor cells and contacted with tumor cells closely. Some of them even encircled tumor cells. There were many varicosities aligned on the nerve fibers like beads. They were also closely related to tumor cells. In the co-culture group, about 63 % and 67 % of DRG co-cultured with esophageal and cardiac tumor blocks respectively extended enormous processes, especially on the side adjacent to the tumor, whereas in the control group (without tumor blocks), no processes grew out. CONCLUSION:Esophageal and cardiac carcinomas may be innervated by peptidergic nerve fibers, and they can induce neurons of DRG to extend processes in vitro.Lü SH, Zhou Y, Que HP, Liu SJ. Peptidergic innervation of human esophageal and cardiac carcinoma. World J Gastroenterol 2003; 9(3): 399-403

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“…32 In general, nerve fibers have been rarely observed in human tumors. [33][34][35] Interestingly, in adrenal cortical tumors, also known to express NPY receptors, 10 nerve fibers have been identified that were also shown to contain NPY. 35 These reports, together with the present results, demonstrate that NPY-positive nerve fibers can grow into certain human tumors.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

Körner

Waser

Reubi

2005

Intl Journal of Cancer

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Numerous peptide receptors are overexpressed in human cancer, permitting in vivo tumor targeting. Among such receptors, those for the neurotransmitter neuropeptide Y (NPY) are overexpressed in various tumors. Since NPY can play a role in the kidney, NPY receptor expression and/or endogenous production of peptides of the NPY family (NPY, PYY, PP) were evaluated in 40 renal cell carcinomas (RCCs) and 18 nephroblastomas. NPY receptor protein expression was investigated by in vitro autoradiography using 125 I-labeled PYY in competition with NPY receptor subtype-selective analogs. NPY, PYY and PP production was assessed immunohistochemically. Fifty-six percent of RCCs expressed the Y1 receptor subtype in moderate density, and 80% of nephroblastomas expressed Y1 and Y2 subtypes in moderate to high density. Y1 was also highly expressed in intratumoral blood vessels. In selected cases, NPY was observed in nerve fibers in close association with intratumoral blood vessels and in the vicinity of tumor cells, while no PYY or PP was detected immunohistochemically in these sites. NPY receptors on renal tumor cells and tumor blood vessels may therefore be the molecular targets of endogenous NPY released by intratumoral nerve fibers. With regard to clinical applications, NPY receptors may act as in vivo targets for receptor-directed therapy of RCCs and nephroblastomas for which alternative therapeutic approaches are still required. ' 2005 Wiley-Liss, Inc.Key words: NPY receptor; renal cell carcinoma; nephroblastoma; receptor autoradiography Peptide hormone receptors are overexpressed in a wide variety of human tumors.1 Like other cell surface molecules, these receptors become increasingly important for clinical applications. In particular, they allow receptor-targeted tumor imaging and therapy with corresponding peptide hormone analogs. For instance, scintigraphy using the somatostatin analog Octreoscan is highly sensitive at detecting gastroenteropancreatic neuroendocrine tumors which express somatostatin receptors in high amounts.2,3 Moreover, targeted radiotherapy of these tumors with 90 Y-or 177 Lu-labeled somatostatin analogs is also promising. 4,5 Another peptide hormone receptor family with a potential future role in this field is the NPY receptor family. It belongs to the G protein-coupled receptor superfamily and comprises various subtypes. Subtypes Y1, Y2, Y4 and Y5 are expressed in humans. 6 They are present mainly in the central and peripheral nervous systems as well as other tissues, such as the cardiovascular system. Their physiologic ligands are the neurotransmitter NPY and the 2 hormones PYY and PP. Among many other sites, NPY has been localized to perivascular nerves in the human kidney. 7 NPY receptors may also play a role in human neoplasia. High incidence rates of subtypes Y1 and Y2 were found in tumors related to steroid hormone metabolism (adrenal cortical tumors, ovarian sex cord-stromal tumors, breast carcinomas), 8,9 in neuroendocrine tumors (pheochromocytomas and paragangliomas) 10

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Nerve fibers in tumors of the human urinary bladder

Cited by 43 publications

References 38 publications

The clinicopathological significance of neurogenesis in breast cancer

The clinicopathological significance of neurogenesis in breast cancer

Peptidergic innervation of human esophageal and cardiac carcinoma

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

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