A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models

Autor(es)

Amaral, Robson ^[1] ; Zimmermann, Maike ^[2] ; Ma, Ai-Hong ^[3] ; Zhang, Hongyong ^[2] ; Swiech, Kamilla ^[1] ; Pan, Chong-Xian ^{[2, 4, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-14040903 Sao Paulo - Brazil

^[2] Univ Calif Davis, Sch Med, Div Hematol & Oncol, Dept Internal Med, Sacramento, CA 95817 - USA

^[3] Univ Calif Davis, Sch Med, UC Davis Comprehens Canc Ctr, Dept Urol, Sacramento, CA 95817 - USA

^[4] VA Northern Calif Hlth Care Syst, Mather, CA 95655 - USA

^[5] Harvard Med Sch, Dept Fac Med, West Roxbury, MA 02115 - USA

• Tipo de documento: Artigo Científico
• Fonte: CANCERS; v. 12, n. 5 MAY 2020.
• Citações Web of Science: 0

Resumo

Patient-derived xenograft (PDX) models allow for personalized drug selection and the identification of drug resistance mechanisms in cancer cells. However, PDX models present technical disadvantages, such as long engraftment time, low success rate, and high maintenance cost. On the other hand, tumor spheroids are emerging as an in vitro alternative model that can maintain the phenotype of cancer cells long enough to perform all assays and predict a patient's outcome. The present work aimed to describe a simple, reproducible, and low-cost 3D in vitro culture method to generate bladder tumor spheroids using human cells from PDX mice. Cancer cells from PDX BL0293 and BL0808 models, previously established from advanced bladder cancer, were cultured in 96-well round-bottom ultra-low attachment (ULA) plates with 5% Matrigel and generated regular and round-shaped spheroids (roundness > 0.8) with a diameter larger than 400 mu m and a hypoxic core (a feature related to drug resistance in solid tumors). The responses of the tumor spheroids to the antineoplastic drugs cisplatin, gemcitabine, and their combination were similar to tumor responses in in vivo studies with PDX BL0293 and BL0808 mice. Therefore, the in vitro 3D model using PDX tumor spheroids appears as a valuable tool that may predict the outcome of in vivo drug-screening assays and represents a low-cost strategy for such purpose. (AU)

• Processo FAPESP: 15/05102-1 - Análise comparativa de diferentes sistemas de cultivo tridimensionais para o estabelecimento de um modelo in vitro de câncer de bexiga para testes citotoxicológicos
• Beneficiário: Robson Luis Ferraz do Amaral
• Linha de fomento: Bolsas no Brasil - Doutorado Direto