Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar
Ano de defesa: | 2014 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Biologia Celular e Molecular
|
Departamento: |
Faculdade de Bioci?ncias
|
País: |
BR
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.pucrs.br/tede2/handle/tede/5511 |
Resumo: | Lung cancer is the most commonly diagnosed type of cancer and the leading cause of cancer related mortality in the world, causing nearly one million deaths per year. Among all histological types, adenocarcinoma is the most frequent one (75-80%). Gastrin-releasing peptide (GRP) is considered to be a mitogen, capable of inducing cell proliferation, since it is involved in fetal lung development. This neuropeptide had its effect on tumor growth first identified in human cells of small cell lung cancer, acting as an autocrine growth factor for tumor tissues by binding to its receptor GRPR. The receptor has been found in many tumor types such as prostate, breast, stomach, pancreas and colon. Moreover, this peptide acts as a morphogen, in angiogenesis and is related to inflammatory processes and in the regulation of cells of the immune system. Furthermore, asymptomatic smokers have high levels of GRP in bronchoalveolar lavage and urine. However, little is known about its effects in tumorigenesis and metastasis, and which molecular mechanisms and signaling pathways are responsible for the effects found. Our group demonstrated recently that GRP could act as a chemotactic molecule for neutrophils. Thus, we hypothesized that GRP could be also a chemotactic stimulus to tumor cells expressing the GRPR. In this study, we tested this hypothesis by examining the effect of GRP on proliferation, survival and migration of cells from the adenocarcinoma cell line A549, seeking to identify the mechanisms of action of this peptide. These cells express high levels of GRPR and treatment with GRP leads to activation of kinases such as AKT and ERK1/2 that are involved in the cellular processes mentioned. Our results suggest that GRP is a migratory stimulus to these cells without evidence of significant effect on their proliferation or survival to treatment with the chemotherapy drug cisplatin (CDDP). Nonetheless, they become more sensitive to CDDP when the drug is combined with a GRPR antagonist. Thus, we believe that future studies should consider a possible role for GRP in metastasis of NSCLC. |
id |
P_RS_c4f120287a53cc44b01f7452f7d7d645 |
---|---|
oai_identifier_str |
oai:tede2.pucrs.br:tede/5511 |
network_acronym_str |
P_RS |
network_name_str |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
repository_id_str |
|
spelling |
Bonorino, CristinaCPF:40887987087http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4780858U3CPF:83482300097http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4468382P6Jaeger, Nat?lia2015-04-14T14:51:37Z2014-12-182014-12-10JAEGER, Nat?lia. Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar. 2014. 72 f. Disserta??o (Mestrado em Biologia Celular e Molecular) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2014.http://tede2.pucrs.br/tede2/handle/tede/5511Lung cancer is the most commonly diagnosed type of cancer and the leading cause of cancer related mortality in the world, causing nearly one million deaths per year. Among all histological types, adenocarcinoma is the most frequent one (75-80%). Gastrin-releasing peptide (GRP) is considered to be a mitogen, capable of inducing cell proliferation, since it is involved in fetal lung development. This neuropeptide had its effect on tumor growth first identified in human cells of small cell lung cancer, acting as an autocrine growth factor for tumor tissues by binding to its receptor GRPR. The receptor has been found in many tumor types such as prostate, breast, stomach, pancreas and colon. Moreover, this peptide acts as a morphogen, in angiogenesis and is related to inflammatory processes and in the regulation of cells of the immune system. Furthermore, asymptomatic smokers have high levels of GRP in bronchoalveolar lavage and urine. However, little is known about its effects in tumorigenesis and metastasis, and which molecular mechanisms and signaling pathways are responsible for the effects found. Our group demonstrated recently that GRP could act as a chemotactic molecule for neutrophils. Thus, we hypothesized that GRP could be also a chemotactic stimulus to tumor cells expressing the GRPR. In this study, we tested this hypothesis by examining the effect of GRP on proliferation, survival and migration of cells from the adenocarcinoma cell line A549, seeking to identify the mechanisms of action of this peptide. These cells express high levels of GRPR and treatment with GRP leads to activation of kinases such as AKT and ERK1/2 that are involved in the cellular processes mentioned. Our results suggest that GRP is a migratory stimulus to these cells without evidence of significant effect on their proliferation or survival to treatment with the chemotherapy drug cisplatin (CDDP). Nonetheless, they become more sensitive to CDDP when the drug is combined with a GRPR antagonist. Thus, we believe that future studies should consider a possible role for GRP in metastasis of NSCLC.O c?ncer de pulm?o ? o tipo de c?ncer que mais comumente diagnosticado e o que mais mata no mundo levando a quase 1 milh?o de mortes por ano. Entre todos os tipos histol?gicos, o adenocarcinoma ? o mais frequente (75-80%). O pept?deo liberador de gastrina (GRP) ? considerado um agente mitog?nico, capaz de induzir a prolifera??o celular, uma vez que est? envolvido no desenvolvimento fetal dos pulm?es. Este pept?deo teve sua a??o sobre o crescimento tumoral primeiramente identificada em c?lulas humanas de c?ncer de pulm?o de pequenas c?lulas, atuando como fator aut?crino de crescimento de tecidos e tumores atrav?s da liga??o ao seu receptor GRPR. Este receptor foi encontrado em diversos tipos de tumores como pr?stata, mama, est?mago, p?ncreas e c?lon. Al?m disso, este pept?deo atua como um morf?geno, na angiog?nese e, est? relacionado a processos inflamat?rios e na regula??o de c?lulas do sistema imune. E, fumantes assintom?ticos possuem altos n?veis de GRP no lavado broncoalveolar e na urina. No entanto, pouco se conhece sobre os seus efeitos na tumorig?nese e met?stase e, quais os mecanismos moleculares e as vias de sinaliza??o que s?o respons?veis pelos efeitos encontrados. Nosso grupo demonstrou, recentemente, que o GRP pode atuar como uma mol?cula quimiot?tica para neutr?filos. Desta forma, hipotetizamos que o GRP poderia constituir num estimulo quimiot?tico tamb?m para as c?lulas tumorais que express?o o GRPR. Neste trabalho, testamos essa hip?tese, analisando o efeito do GRP sobre a prolifera??o, sobreviv?ncia e migra??o de c?lulas da linhagem de adenocarcinoma A549, buscando identificar mecanismos de a??o desse pept?deo. Esta linhagem expressa altos n?veis de GRPR. O tratamento com GRP leva a ativa??o de quinases como a AKT e ERK1/2 que est?o envolvidas nestes processos celulares. Nossos resultados sugerem que o GRP ? principalmente um est?mulo migrat?rio para estas c?lulas, sem evid?ncias de efeito significativo sobre a sua prolifera??o ou sobreviv?ncia ao tratamento com a droga quimioter?pica cisplatina, mas tornam-se mais sens?veis quando a droga ? combinada com um antagonista do GRPR. Dessa forma, acreditamos que estudos futuros devam considerar um poss?vel papel para o GRP na met?stase.Made available in DSpace on 2015-04-14T14:51:37Z (GMT). No. of bitstreams: 1 464249.pdf: 13663409 bytes, checksum: 370383758e5762e6645f52a510e7dfab (MD5) Previous issue date: 2014-12-10application/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/16599/464249.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Biologia Celular e MolecularPUCRSBRFaculdade de Bioci?nciasBIOLOGIA CELULARBIOLOGIA MOLECULARADENOCARCINOMANEOPLASIASPEPT?DEO LIBERADOR DE GASTRINACNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERALInvestiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonarinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis819824693009663736060060036528317262667714info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAIL464249.pdf.jpg464249.pdf.jpgimage/jpeg3572http://tede2.pucrs.br/tede2/bitstream/tede/5511/3/464249.pdf.jpg479e6059c31a2987ae0cb91b17a23855MD53TEXT464249.pdf.txt464249.pdf.txttext/plain122005http://tede2.pucrs.br/tede2/bitstream/tede/5511/2/464249.pdf.txt6ab7823e7eb68a2d08991936d22300e2MD52ORIGINAL464249.pdfapplication/pdf13663409http://tede2.pucrs.br/tede2/bitstream/tede/5511/1/464249.pdf370383758e5762e6645f52a510e7dfabMD51tede/55112015-05-14 11:40:31.376oai:tede2.pucrs.br:tede/5511Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2015-05-14T14:40:31Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
title |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
spellingShingle |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar Jaeger, Nat?lia BIOLOGIA CELULAR BIOLOGIA MOLECULAR ADENOCARCINOMA NEOPLASIAS PEPT?DEO LIBERADOR DE GASTRINA CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
title_full |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
title_fullStr |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
title_full_unstemmed |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
title_sort |
Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar |
author |
Jaeger, Nat?lia |
author_facet |
Jaeger, Nat?lia |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonorino, Cristina |
dc.contributor.advisor1ID.fl_str_mv |
CPF:40887987087 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4780858U3 |
dc.contributor.authorID.fl_str_mv |
CPF:83482300097 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4468382P6 |
dc.contributor.author.fl_str_mv |
Jaeger, Nat?lia |
contributor_str_mv |
Bonorino, Cristina |
dc.subject.por.fl_str_mv |
BIOLOGIA CELULAR BIOLOGIA MOLECULAR ADENOCARCINOMA NEOPLASIAS PEPT?DEO LIBERADOR DE GASTRINA |
topic |
BIOLOGIA CELULAR BIOLOGIA MOLECULAR ADENOCARCINOMA NEOPLASIAS PEPT?DEO LIBERADOR DE GASTRINA CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Lung cancer is the most commonly diagnosed type of cancer and the leading cause of cancer related mortality in the world, causing nearly one million deaths per year. Among all histological types, adenocarcinoma is the most frequent one (75-80%). Gastrin-releasing peptide (GRP) is considered to be a mitogen, capable of inducing cell proliferation, since it is involved in fetal lung development. This neuropeptide had its effect on tumor growth first identified in human cells of small cell lung cancer, acting as an autocrine growth factor for tumor tissues by binding to its receptor GRPR. The receptor has been found in many tumor types such as prostate, breast, stomach, pancreas and colon. Moreover, this peptide acts as a morphogen, in angiogenesis and is related to inflammatory processes and in the regulation of cells of the immune system. Furthermore, asymptomatic smokers have high levels of GRP in bronchoalveolar lavage and urine. However, little is known about its effects in tumorigenesis and metastasis, and which molecular mechanisms and signaling pathways are responsible for the effects found. Our group demonstrated recently that GRP could act as a chemotactic molecule for neutrophils. Thus, we hypothesized that GRP could be also a chemotactic stimulus to tumor cells expressing the GRPR. In this study, we tested this hypothesis by examining the effect of GRP on proliferation, survival and migration of cells from the adenocarcinoma cell line A549, seeking to identify the mechanisms of action of this peptide. These cells express high levels of GRPR and treatment with GRP leads to activation of kinases such as AKT and ERK1/2 that are involved in the cellular processes mentioned. Our results suggest that GRP is a migratory stimulus to these cells without evidence of significant effect on their proliferation or survival to treatment with the chemotherapy drug cisplatin (CDDP). Nonetheless, they become more sensitive to CDDP when the drug is combined with a GRPR antagonist. Thus, we believe that future studies should consider a possible role for GRP in metastasis of NSCLC. |
publishDate |
2014 |
dc.date.available.fl_str_mv |
2014-12-18 |
dc.date.issued.fl_str_mv |
2014-12-10 |
dc.date.accessioned.fl_str_mv |
2015-04-14T14:51:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
JAEGER, Nat?lia. Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar. 2014. 72 f. Disserta??o (Mestrado em Biologia Celular e Molecular) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2014. |
dc.identifier.uri.fl_str_mv |
http://tede2.pucrs.br/tede2/handle/tede/5511 |
identifier_str_mv |
JAEGER, Nat?lia. Investiga??o do efeito proliferativo e migrat?rio do pept?deo liberador de gastrina (GRP) sobre uma linhagem de adenocarcinoma pulmonar. 2014. 72 f. Disserta??o (Mestrado em Biologia Celular e Molecular) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2014. |
url |
http://tede2.pucrs.br/tede2/handle/tede/5511 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
8198246930096637360 |
dc.relation.confidence.fl_str_mv |
600 600 |
dc.relation.department.fl_str_mv |
36528317262667714 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
dc.publisher.program.fl_str_mv |
Programa de P?s-Gradua??o em Biologia Celular e Molecular |
dc.publisher.initials.fl_str_mv |
PUCRS |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Faculdade de Bioci?ncias |
publisher.none.fl_str_mv |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) instacron:PUC_RS |
instname_str |
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
instacron_str |
PUC_RS |
institution |
PUC_RS |
reponame_str |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
collection |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
bitstream.url.fl_str_mv |
http://tede2.pucrs.br/tede2/bitstream/tede/5511/3/464249.pdf.jpg http://tede2.pucrs.br/tede2/bitstream/tede/5511/2/464249.pdf.txt http://tede2.pucrs.br/tede2/bitstream/tede/5511/1/464249.pdf |
bitstream.checksum.fl_str_mv |
479e6059c31a2987ae0cb91b17a23855 6ab7823e7eb68a2d08991936d22300e2 370383758e5762e6645f52a510e7dfab |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
repository.mail.fl_str_mv |
biblioteca.central@pucrs.br|| |
_version_ |
1796793210274578432 |