Early Patterning of the Nervous System

This section describes the influence of the hedgehog and BMP pathways on the early dorso-ventral patterning of the nervous system. Understanding the geometry of neurulation is prerequisite for understanding the mechanisms of dorso-ventral patterning of the nervous system. In the previous section, it was described that the neural plate invaginates along its anterio-posterior axis and successively forms the neural groove and neural tube 46 . During the entire process of neurulation, the notochord...

Neuronal Activity in Tumor Tissue

Z nker Witten Frank Entschiaden Witten Basel Freiburg Paris London New York Bangalore Bangkok Singapore Tokyo Sydney Progress in Experimental Tumor Research Founded 1960 by F. Homburger, Cambridge, Mass. Institute of Immunology University of Witten Herdecke Stockumer Strasse 10 DE-58448 Witten Institute of Immunology University of Witten Herdecke Stockumer Strasse 10 DE-58448 Witten Library of Congress Cataloging-in-Publication Data Neuronal activity in tumor tissue volume editors, Kurt...

Axon Guidance Molecules

In addition to controlling indirectly tumor cell survival by regulating angiogenesis, chemotropic axon guidance molecules may also exert a direct action on proliferation and apoptosis 3 . Thus, SEMA3B transfection in lung cancer cell lines or application of exogenous soluble SEMA3B ectodomain decrease colony formation and induces apoptosis. An anti-proliferative activity of SEMA3B has been shown for breast cancer cell lines. Likewise, VEGF binding to neuropilin-1 is required for the survival of...

Biogenic Amines

Epinephrine, Norepinephrine and Dopamine Catecholamines have strong, however, diverse impacts on the function of various leukocytes, and lymphatic organs are directly innervated by noradrenergic nerve fibers 2 . On the one hand, the migratory activity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells is enhanced by norepinephrine 3 . Furthermore, mice that are deficient in the dopamine -hydroxylase, an enzyme which converts dopamine to norepinephrine, have an impaired T-cell...

Conclusion and Outlook

The previous paragraphs have shown that many proteins that were first identified in the nervous system later turned out to be expressed in various other tissues. Hence, it is important to be aware that the term 'neural' in these cases is only a historical one - a fact that will most likely apply to more and more antigens in the future. Looking at the function of the proteins mentioned, they fall into (overlapping) categories like (i) maintenance and repair, (ii) directing migration, (iii)...

Neuronal Migration and Differentiation

Once the different regions and subdivision of the developing nervous system are specified, the newly generated precursors from the matrix zone are set and ready for migration 8, 56 . There are two types of migration, the radial and the tangential migration. In the context of radial migration, cells migrate from the matrix zone along the radial glia scaffold towards the surface of the developing nervous system. In contrast, tangential migration is characterized by a direction of cell migration...

Conclusion

Here some examples of GPCR have been presented that are known to be frequently up-regulated in cancer cells and to mediate major cellular pathways involved in tumorigenesis and in nerve development. They have been chosen because their corresponding natural agonists may possess direct suppressive properties on neoneurogenesis, as it is the case for SST autocrine paracrine growth factors properties in tumor cells that may also promote nerve development in the tumor microenvironment. This is the...

Adrenergic Receptor Signaling and Lung Adenocarcinoma

Adenocarcinoma of the lung is the leading histological type of lung cancer in men and women. Risk factors for the development of this cancer are strikingly similar to risk factors for cardiovascular disease, namely smoking and a high fat diet 18 . The carcinogenic nitrosamines n-nitrosonornicotine (NNN) and (NNK) are formed from nicotine (fig. 1) in the presence of nitrosating agents during the processing of tobacco and in the mammalian organism. Each of these nitrosamines acts systemically,...

Epidemiological Aspects

Since 1926, it has been assumed that psychosocial factors influence the cancer incidence and tumor progression 27 . This argument is difficult to verify scientifically, as the individual perception of environmental influences widely varies. However, it seems that negative emotions such as stress, anxiety or depression facilitate tumor progression. This has been shown largely by epi-demiological studies in two directions. The first direction aims at pharmacological evidences. Stress, anxiety, or...

Small Cell Lung Carcinoma

SCLC is a highly aggressive type of lung cancer that expresses neuroendocrine markers such as 5-hytroxytryptamine (5-HT, serotonin), mammalian bombesin (MB), calcitonin, neuron specific enolase, and others. SCLC does not harbor activating point mutations in K-ras, but frequently demonstrates amplification of c-myc and mutations in the retinoblastoma and p53 genes 51 . The majority of SCLCs are though to have derived from the epithelial lining cells of large airways while a small population of...

Enteric Nervous System

The enteric nervous system, the intrinsic innervation of the gastrointestinal tract, consists of two main ganglionated and interconnecting plexi, the Meissner plexus in the submucosal layer and the Auerbach plexus between the inner circular and the outer longitudinal muscle layer 55 . Functionally the enteric nervous system is more or less independent of the central nervous system with intrinsic primary afferent neurons, interneurons and motor neurons 56, 57 . It regulates complex peristalsis,...

In Vivo Evidence for a Role for Axon Guidance Molecules in Cancers

To data, most studies on axon guidance molecules in tumorigenesis have focused on expression profiles and in vitro assays and only a few in vivo evidence has been obtained. SEMA3F-transfected melanoma cells injected into nude mice do not become metastatic 28 . This could be explained by an inhibitory action of SEMA3F on endothelial cell invasion and or tumor cell migration. A targeted mutation of mouse ROBO1 was generated by deletion of exon 2, mimicking a deletion that naturally occurs in...

Compartments of the Peripheral Nerve

Peripheral nerves are enclosed by three connective tissue compartments, the epineurium, perineurium and endoneurium, which protect the nerve fibers along their pathway to their targets against external stimuli and which guarantee a controlled microenvironment for the axons and Schwann cells. Peripheral nerves have their own vascular supply - the vasa nervorum - composed of the epidural vascular plexus providing endoneural microvessels. Due to the characteristic composition of the three...

In Remembrance of Fritz Bender Esq 19071986

At this 100th anniversary of Fritz Benders birthday, it is my honorable duty, and soulful wish to reminisce and contemplate the heritage he generously bestowed upon us. Fritz Bender was born in Heidelberg, the romantic and historical town on the banks of the Neckar. It is here, as well as in many cities strewn across the country, that one can find signs of his work as a unique master of the building trade. City council buildings in Mannheim, and Munich still bear evidence of his skill as...

References

1 Akert K, Sandri C, Weibel ER, Peper K, Moor H The fine structure of the perineural endothelium. Cell Tissue Res 1976 165 281-295. 2 Bush MS, Allt G Distribution of anionic sites on the perineurium. J Anat 1990 181 79-87. 3 Todd BA, Inman C, Sedgwick EM, Abbott NJ Ionic permeability of the frog sciatic nerve perineurium parallel studies of potassium and lanthanum penetration using electrophysiological and electron microscopic techniques. J Neurocytol 2000 29 551-567. 4 Pummi KP, Heape AM,...

Neuronal Antigens

The expression of neuronal antigens is controlled by different regulators, one factor leading to up-regulation being mammalian achaete-scute homolog-1 (Mash-1 or hAsh-1) which is expressed in neuronal and neuroendocrine tissues. Strict suppression of several neuronal antigens in non-neuronal tissues is realized on the transcriptional level through the zinc-finger transcription factor neuron-restrictive silencer factor (NRSF) and its co-repressors mSin3A and CoREST which bind to the mammalian...

Major Signaling Pathways in Neuronal Development

The Wnt pathway has important functions for the development of all metazoan organisms, as reflected by its name, which is a contraction of Wingless, a Drosophila segment polarity gene, and its murine homolog Int-1, a proto-oncogene 18, 19 . The pathway is initiated by the binding of a Wnt ligand to its receptor complex, which is composed of a Frizzled-family member and LRP-5 6, a member of the low-density lipoprotein (LDL) receptor family 23 . In mammals, there are about 20 different Wnt...

Expression of Chemotropic Axon Guidance Molecules in Cancer Cells

Over the last few years, the expression of chemotropic axon guidance molecules in a variety of cancer cell lines and tumors has been thoroughly Fig. 3. Netrin-1 and its receptors. Netrin-1 contains a laminin N-terminal domain, two laminin EGF-like domain and a netrin C-terminal domain. Several transmembrane netrin-1 receptors are known. DCC, UNC5A-UNC5D and the adenosine receptor A2b, a seven membrane domain receptor. Fig. 3. Netrin-1 and its receptors. Netrin-1 contains a laminin N-terminal...

Neuro Neoplastic Interaction

High levels of expression of neuropeptides receptors have been reported in several types of human cancers, which represents a molecular basis for a novel concept of peptide receptor targeting of tumors with potential clinical applications in oncology. Such paradigm is well-illustrated for somatostatin (SST) and SST receptors, that have been extensively studied in the context of in vivo targeting of neuroendocrine tumors and for the development of a receptor-targeted radiotherapy, using for...

Myelinating Schwann Cell

Myelin Sheath Measurement

Phylogenetically, myelinating Schwann cells appear first in gnastostomes. Agnatha do not have myelinating glial cells at all 23, 24 . Myelination of the axons is a prerequisite for rapid saltatory signal propagation in the neuronal network. During the ontogenetic development myelination of axons occurs in complex interactive networks where neurons and glial cells are dependent on reciprocal signals in a time and a space specific manner 25 . The molecular analysis of the myelination process is a...

Blood Nerve Barrier

The blood-nerve barrier is established in two locations First, the perineurium, which protects the nerve fibers against diffusion of substances from the external environment into the nerve fascicles second, the endoneurial capillaries with their tight junctions avoiding the direct transport of substances from the blood circulation into the endoneurium. As we know from experimental work, the expression of special tight junction proteins in the perineurial cells and capillary endothelial cells...