Type-I Collagen/Collagenase Modulates the 3D Structure and Behavior of Glioblastoma Spheroid Models

Autor(es)

Calori, Italo Rodrigo ; Alves, Samara Rodrigues ; Bi, Hong ; Tedesco, Antonio Claudio

• Tipo de documento: Artigo Científico
• Fonte: ACS APPLIED BIO MATERIALS; v. 5, n. 2, p. 11-pg., 2022-02-21.

Resumo

three-dimensional culture models that resemble and mimic the complexity of the dense and hypoxic cancer microenvironment. However, in brain tumor studies, a variety of glioblastoma multiforme (GBM) cell lines only self-assemble into loose cellular aggregates, lacking the properties of actual glioma tumors in humans. In this study, we used type-I collagen as an extracellular matrix component to promote the compaction of GBM aggregates forming tight spheroids to understand how collagen influences the properties of tumors, such as their growth, proliferation, and invasion, and collagenase to promote collagen degradation. The GBM cell lines U87MG, T98G, and A172, as well as the medulloblastoma cell line UW473, were used as standard cell lines that do not spontaneously self-assemble into spheroids, and GBM U251 was used as a self-assembling cell line. According to the findings, all cell lines formed tight spheroids at collagen concentrations higher than 15.0 mu g mL(-1). Collagen was distributed along the spheroid, similarly to that observed in invasive GBM tumors, and decreased cell migration with no effect on the cellular uptake of small active molecules, as demonstrated by uptake studies using the photosensitizer verteporfin. The enzymatic cleavage of collagen affected spheroid morphology and increased cell migration while maintaining cell viability. Such behaviors are relevant to the physiological models of GBM tumors and are useful for better understanding cell migration and the in vivo infiltration path, drug screening, and kinetics of progression of GBM tumors. (AU)

• Processo FAPESP: 20/04507-6 - "hidrogéis confinados em matriz impressa 3d para a entrega controlada e sítio-específica de ingenol-3-dodecanoato e fluorocromo visando fotodiagnóstico e terapia de tumores cerebrais"
• Beneficiário: Italo Rodrigo Calori
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/50181-1 - Utilização de nanocarreadores contendo fármacos fotossensibilizantes e outros ativos aplicados à terapia celular e tratamento de patologias do sistema nervoso central
• Beneficiário: Antonio Claudio Tedesco
• Modalidade de apoio: Auxílio à Pesquisa - Temático