Spatio-temporal modeling and live-cell imaging of proteolysis in the 4D microenvironment of breast cancer.
Cancer Metastasis Rev
; 38(3): 445-454, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31605250
ABSTRACT
Cells grown in three dimensions (3D) within natural extracellular matrices or synthetic scaffolds more closely recapitulate the phenotype of those cells within tissues in regard to normal developmental and pathobiological processes. This includes degradation of the surrounding stroma as the cells migrate and invade through the matrices. As 3D cultures of tumor cells predict efficacy of, and resistance to, a wide variety of cancer therapies, we employed tissue-engineering approaches to establish 3D pathomimetic avatars of human breast cancer cells alone and in the context of both their cellular and pathochemical microenvironments. We have shown that we can localize and quantify key parameters of malignant progression by live-cell imaging of the 3D avatars over time (4D). One surrogate for changes in malignant progression is matrix degradation, which can be localized and quantified by our live-cell proteolysis assay. This assay is predictive of changes in spatio-temporal and dynamic interactions among the co-cultured cells and changes in viability, proliferation, and malignant phenotype. Furthermore, our live-cell proteolysis assay measures the effect of small-molecule inhibitors of proteases and kinases, neutralizing or blocking antibodies to cytokines and photodynamic therapy on malignant progression. We suggest that 3D/4D pathomimetic avatars in combination with our live-cell proteolysis assays will be a useful preclinical screening platform for cancer therapies. Our ultimate goal is to develop 3D/4D avatars from an individual patient's cancer in which we can screen "personalized medicine" therapies using changes in proteolytic activity to quantify therapeutic efficacy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Carcinoma Ductal de Mama
/
Carcinoma Intraductal no Infiltrante
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Metastasis Rev
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos