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A 3D fibrous scaffold inducing tumoroids: a platform for anticancer drug development.
Girard, Yvonne K; Wang, Chunyan; Ravi, Sowndharya; Howell, Mark C; Mallela, Jaya; Alibrahim, Mahmoud; Green, Ryan; Hellermann, Gary; Mohapatra, Shyam S; Mohapatra, Subhra.
Afiliación
  • Girard YK; Department of Molecular Medicine, University of South Florida, Tampa, Florida, United States of America ; USF Nanomedicine Research Center, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
PLoS One ; 8(10): e75345, 2013.
Article en En | MEDLINE | ID: mdl-24146752
The development of a suitable three dimensional (3D) culture system for anticancer drug development remains an unmet need. Despite progress, a simple, rapid, scalable and inexpensive 3D-tumor model that recapitulates in vivo tumorigenesis is lacking. Herein, we report on the development and characterization of a 3D nanofibrous scaffold produced by electrospinning a mixture of poly(lactic-co-glycolic acid) (PLGA) and a block copolymer of polylactic acid (PLA) and mono-methoxypolyethylene glycol (mPEG) designated as 3P. Cancer cells cultured on the 3P scaffold formed tight irregular aggregates similar to in vivo tumors, referred to as tumoroids that depended on the topography and net charge of the scaffold. 3P scaffolds induced tumor cells to undergo the epithelial-to-mesenchymal transition (EMT) as demonstrated by up-regulation of vimentin and loss of E-cadherin expression. 3P tumoroids showed higher resistance to anticancer drugs than the same tumor cells grown as monolayers. Inhibition of ERK and PI3K signal pathways prevented EMT and reduced tumoroid formation, diameter and number. Fine needle aspirates, collected from tumor cells implanted in mice when cultured on 3P scaffolds formed tumoroids, but showed decreased sensitivity to anticancer drugs, compared to tumoroids formed by direct seeding. These results show that 3P scaffolds provide an excellent platform for producing tumoroids from tumor cell lines and from biopsies and that the platform can be used to culture patient biopsies, test for anticancer compounds and tailor a personalized cancer treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Poliglicólico / Regulación Neoplásica de la Expresión Génica / Ácido Láctico / Técnicas de Cultivo de Tejidos / Andamios del Tejido / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Poliglicólico / Regulación Neoplásica de la Expresión Génica / Ácido Láctico / Técnicas de Cultivo de Tejidos / Andamios del Tejido / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos