A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines

Autores
Romo, Ana; Guo, Yu; Rodríguez, Tania Melina; Dewey, Ricardo
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
TGF-beta signaling pathway is a key regulator of cancer progression, par ticularly incolorectal cancer where 90% of microsatellite instable (MSI) tumors exhibitmutations in the TGF-beta receptor type 2 (TGFBR2) gene. Here, we show thatlentiviral mediated overexpression of TGFBR2-SE, a recently discovered solubleisoform of the human TGF-beta type 2 receptor, fused to the human IgG1 Fc fragment(TGFBR2-SE/Fc) reduces in vitro cell proliferation and migration while induces cellcycle arrest and apoptosis in the primary human colorectal cancer derived cell lineHCT116. Moreover, TGFBR2-SE/Fc impairs tumorigenicity of BALB/c nudeathymic mice xenografts, increasing the survival rate of the animals. Tumorsoverexpressing TGFBR2-SE/Fc were considerable smaller or even unable to beestablished as only 3 out of 6 mice developed tumors in the TGFBR2-SE/Fc group.Mechanistically, TGFBR2-SE/Fc downregulates TGF-beta canonical pathway andleads to the activation of tumor suppressor genes such as p21, p57 and p53 aswell as to the inactivation of cell cycle progression elements such as cyclin B1 a ndId1. These findings suggest a strong antitumor activity of TGFBR2-SE/Fc based onblocking TGF-beta signaling pathway and Smad2/3 independent changes in geneexpression supporting the further exploration and development of TGFBR2-SE/Fcas a new biopharmace utical for the treatment of solid tumors.
Fil: Romo, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Guo, Yu. Shanghai Jiao Tong University; China
Fil: Rodríguez, Tania Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Reunión de Sociedades de Biociencias 2020
Virtual
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Fisiología
Materia
TGFBR2-SE/Fc
NUEVA ISOFORMA DE TGFBR2
COLORECTAL CANCER
ANTITUMOR ACTIVITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/264697
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/264697
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell linesRomo, AnaGuo, YuRodríguez, Tania MelinaDewey, RicardoTGFBR2-SE/FcNUEVA ISOFORMA DE TGFBR2COLORECTAL CANCERANTITUMOR ACTIVITYhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3TGF-beta signaling pathway is a key regulator of cancer progression, par ticularly incolorectal cancer where 90% of microsatellite instable (MSI) tumors exhibitmutations in the TGF-beta receptor type 2 (TGFBR2) gene. Here, we show thatlentiviral mediated overexpression of TGFBR2-SE, a recently discovered solubleisoform of the human TGF-beta type 2 receptor, fused to the human IgG1 Fc fragment(TGFBR2-SE/Fc) reduces in vitro cell proliferation and migration while induces cellcycle arrest and apoptosis in the primary human colorectal cancer derived cell lineHCT116. Moreover, TGFBR2-SE/Fc impairs tumorigenicity of BALB/c nudeathymic mice xenografts, increasing the survival rate of the animals. Tumorsoverexpressing TGFBR2-SE/Fc were considerable smaller or even unable to beestablished as only 3 out of 6 mice developed tumors in the TGFBR2-SE/Fc group.Mechanistically, TGFBR2-SE/Fc downregulates TGF-beta canonical pathway andleads to the activation of tumor suppressor genes such as p21, p57 and p53 aswell as to the inactivation of cell cycle progression elements such as cyclin B1 a ndId1. These findings suggest a strong antitumor activity of TGFBR2-SE/Fc based onblocking TGF-beta signaling pathway and Smad2/3 independent changes in geneexpression supporting the further exploration and development of TGFBR2-SE/Fcas a new biopharmace utical for the treatment of solid tumors.Fil: Romo, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Guo, Yu. Shanghai Jiao Tong University; ChinaFil: Rodríguez, Tania Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaReunión de Sociedades de Biociencias 2020VirtualArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/264697A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines; Reunión de Sociedades de Biociencias 2020; Virtual; Argentina; 2020; 115-1150025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2020/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:21:45Zoai:ri.conicet.gov.ar:11336/264697instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-05 10:21:45.915CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
title A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
spellingShingle A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
Romo, Ana
TGFBR2-SE/Fc
NUEVA ISOFORMA DE TGFBR2
COLORECTAL CANCER
ANTITUMOR ACTIVITY
title_short A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
title_full A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
title_fullStr A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
title_full_unstemmed A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
title_sort A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines
dc.creator.none.fl_str_mv Romo, Ana
Guo, Yu
Rodríguez, Tania Melina
Dewey, Ricardo
author Romo, Ana
author_facet Romo, Ana
Guo, Yu
Rodríguez, Tania Melina
Dewey, Ricardo
author_role author
author2 Guo, Yu
Rodríguez, Tania Melina
Dewey, Ricardo
author2_role author
author
author
dc.subject.none.fl_str_mv TGFBR2-SE/Fc
NUEVA ISOFORMA DE TGFBR2
COLORECTAL CANCER
ANTITUMOR ACTIVITY
topic TGFBR2-SE/Fc
NUEVA ISOFORMA DE TGFBR2
COLORECTAL CANCER
ANTITUMOR ACTIVITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv TGF-beta signaling pathway is a key regulator of cancer progression, par ticularly incolorectal cancer where 90% of microsatellite instable (MSI) tumors exhibitmutations in the TGF-beta receptor type 2 (TGFBR2) gene. Here, we show thatlentiviral mediated overexpression of TGFBR2-SE, a recently discovered solubleisoform of the human TGF-beta type 2 receptor, fused to the human IgG1 Fc fragment(TGFBR2-SE/Fc) reduces in vitro cell proliferation and migration while induces cellcycle arrest and apoptosis in the primary human colorectal cancer derived cell lineHCT116. Moreover, TGFBR2-SE/Fc impairs tumorigenicity of BALB/c nudeathymic mice xenografts, increasing the survival rate of the animals. Tumorsoverexpressing TGFBR2-SE/Fc were considerable smaller or even unable to beestablished as only 3 out of 6 mice developed tumors in the TGFBR2-SE/Fc group.Mechanistically, TGFBR2-SE/Fc downregulates TGF-beta canonical pathway andleads to the activation of tumor suppressor genes such as p21, p57 and p53 aswell as to the inactivation of cell cycle progression elements such as cyclin B1 a ndId1. These findings suggest a strong antitumor activity of TGFBR2-SE/Fc based onblocking TGF-beta signaling pathway and Smad2/3 independent changes in geneexpression supporting the further exploration and development of TGFBR2-SE/Fcas a new biopharmace utical for the treatment of solid tumors.
Fil: Romo, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Guo, Yu. Shanghai Jiao Tong University; China
Fil: Rodríguez, Tania Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Reunión de Sociedades de Biociencias 2020
Virtual
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Fisiología
description TGF-beta signaling pathway is a key regulator of cancer progression, par ticularly incolorectal cancer where 90% of microsatellite instable (MSI) tumors exhibitmutations in the TGF-beta receptor type 2 (TGFBR2) gene. Here, we show thatlentiviral mediated overexpression of TGFBR2-SE, a recently discovered solubleisoform of the human TGF-beta type 2 receptor, fused to the human IgG1 Fc fragment(TGFBR2-SE/Fc) reduces in vitro cell proliferation and migration while induces cellcycle arrest and apoptosis in the primary human colorectal cancer derived cell lineHCT116. Moreover, TGFBR2-SE/Fc impairs tumorigenicity of BALB/c nudeathymic mice xenografts, increasing the survival rate of the animals. Tumorsoverexpressing TGFBR2-SE/Fc were considerable smaller or even unable to beestablished as only 3 out of 6 mice developed tumors in the TGFBR2-SE/Fc group.Mechanistically, TGFBR2-SE/Fc downregulates TGF-beta canonical pathway andleads to the activation of tumor suppressor genes such as p21, p57 and p53 aswell as to the inactivation of cell cycle progression elements such as cyclin B1 a ndId1. These findings suggest a strong antitumor activity of TGFBR2-SE/Fc based onblocking TGF-beta signaling pathway and Smad2/3 independent changes in geneexpression supporting the further exploration and development of TGFBR2-SE/Fcas a new biopharmace utical for the treatment of solid tumors.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/264697
A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines; Reunión de Sociedades de Biociencias 2020; Virtual; Argentina; 2020; 115-115
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/264697
identifier_str_mv A novel soluble isoform of the human TGF-β type 2 receptor exerts strong antitumor activity in colorectal cancer-derived cell lines; Reunión de Sociedades de Biociencias 2020; Virtual; Argentina; 2020; 115-115
0025-7680
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2020/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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