Recent studies suggest that secreted proteins in several families of axon guidance molecules, the slits, the semaphorins and the netrins may play important roles in cancers. The expression of many of these proteins is either down-regulated or up-regulated in cancer cell lines and tumors. Several of the corresponding genes are localized on chromosomal regions associated with frequent loss-of-heterozygosity and their promoters are hypermethylated, suggesting that they may act as tumor suppressors. Moreover, many axon guidance proteins were also shown to control the development of the vasculature and may thus control angiogenesis in the tumors. These axon guidance molecules may also control the migration and invasion potential of cancer cells. Lastly, they could stimulate their proliferation and regulate cell death. Thus, axon guidance molecules appear as good targets for the development of novel therapeutic agents for the treatment of malignancy.
{"title":"Chemotropic axon guidance molecules in tumorigenesis.","authors":"Alain Chédotal","doi":"10.1159/000100048","DOIUrl":"https://doi.org/10.1159/000100048","url":null,"abstract":"<p><p>Recent studies suggest that secreted proteins in several families of axon guidance molecules, the slits, the semaphorins and the netrins may play important roles in cancers. The expression of many of these proteins is either down-regulated or up-regulated in cancer cell lines and tumors. Several of the corresponding genes are localized on chromosomal regions associated with frequent loss-of-heterozygosity and their promoters are hypermethylated, suggesting that they may act as tumor suppressors. Moreover, many axon guidance proteins were also shown to control the development of the vasculature and may thus control angiogenesis in the tumors. These axon guidance molecules may also control the migration and invasion potential of cancer cells. Lastly, they could stimulate their proliferation and regulate cell death. Thus, axon guidance molecules appear as good targets for the development of novel therapeutic agents for the treatment of malignancy.</p>","PeriodicalId":49661,"journal":{"name":"Progress in Tumor Research","volume":"39 ","pages":"78-90"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000100048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26620799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skin, musculoskeletal system and all organs of the body are supplied by nerve fibers of the somatic and autonomic nervous system, each of the systems with its specific nerve fiber types, fiber composition, fiber density and targets. Experimental data support the hypothesis that tumor tissue might interact with nerve fibers. The peripheral nervous system possesses an extraordinary cellular equipment to protect the axons against pathological stimuli. Only restricted areas lacking a cellular barrier are weak points within the nervous network. Therefore, this article focuses on the functional morphology of the peripheral nervous system and its regional differences.
{"title":"Organization of peripheral nerves in skin, musculoskeletal system and viscera.","authors":"Monika von Düring, Britta Fricke","doi":"10.1159/000100043","DOIUrl":"https://doi.org/10.1159/000100043","url":null,"abstract":"<p><p>Skin, musculoskeletal system and all organs of the body are supplied by nerve fibers of the somatic and autonomic nervous system, each of the systems with its specific nerve fiber types, fiber composition, fiber density and targets. Experimental data support the hypothesis that tumor tissue might interact with nerve fibers. The peripheral nervous system possesses an extraordinary cellular equipment to protect the axons against pathological stimuli. Only restricted areas lacking a cellular barrier are weak points within the nervous network. Therefore, this article focuses on the functional morphology of the peripheral nervous system and its regional differences.</p>","PeriodicalId":49661,"journal":{"name":"Progress in Tumor Research","volume":"39 ","pages":"30-44"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000100043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26565372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The autonomic nervous system with its two antagonistic branches, the sympathicus and the parasympathicus, regulates the activities of all body functions that are not under voluntary control. While the autonomic regulation of organ functions has been extensively studied, little attention has been given to the potential role of neurohumoral transmission at the cellular level in the development of cancer. Studies conducted by our laboratory first showed that binding of the parasympathetic neurotransmitter, acetylcholine, as well as nicotine or its nitrosated cancer-causing derivative, NNK, to nicotinic acetylcholine receptors comprised of alpha7 subunits activated a mitogenic signal transduction pathway in normal and neoplastic pulmonary neuroendocrine cells. On the other hand, beta-adrenergic receptors (Beta-ARs), which transmit signals initiated by binding of the catecholamine neurotransmitters of the sympathicus, were identified by our laboratory as important regulators of cell proliferation in cell lines derived from human adenocarcinomas of the lungs, pancreas, and breast. The tobacco-specific carcinogen NNK bound with high affinity to Beta1- and Beta2-ARs, thus activating cAMP, protein kinase A, and the transcription factor CREB. Collectively, neurotransmitter receptors of the nicotinic and Beta-adrenergic families appear to regulate cellular functions essential for the development and survival of the most common human cancers.
{"title":"Neurotransmitter receptor-mediated signaling pathways as modulators of carcinogenesis.","authors":"Hildegard M Schuller","doi":"10.1159/000100045","DOIUrl":"https://doi.org/10.1159/000100045","url":null,"abstract":"<p><p>The autonomic nervous system with its two antagonistic branches, the sympathicus and the parasympathicus, regulates the activities of all body functions that are not under voluntary control. While the autonomic regulation of organ functions has been extensively studied, little attention has been given to the potential role of neurohumoral transmission at the cellular level in the development of cancer. Studies conducted by our laboratory first showed that binding of the parasympathetic neurotransmitter, acetylcholine, as well as nicotine or its nitrosated cancer-causing derivative, NNK, to nicotinic acetylcholine receptors comprised of alpha7 subunits activated a mitogenic signal transduction pathway in normal and neoplastic pulmonary neuroendocrine cells. On the other hand, beta-adrenergic receptors (Beta-ARs), which transmit signals initiated by binding of the catecholamine neurotransmitters of the sympathicus, were identified by our laboratory as important regulators of cell proliferation in cell lines derived from human adenocarcinomas of the lungs, pancreas, and breast. The tobacco-specific carcinogen NNK bound with high affinity to Beta1- and Beta2-ARs, thus activating cAMP, protein kinase A, and the transcription factor CREB. Collectively, neurotransmitter receptors of the nicotinic and Beta-adrenergic families appear to regulate cellular functions essential for the development and survival of the most common human cancers.</p>","PeriodicalId":49661,"journal":{"name":"Progress in Tumor Research","volume":"39 ","pages":"45-63"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000100045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26565373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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