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Tumour cell invasiveness and response to chemotherapeutics in adipocyte invested 3D engineered anisotropic collagen scaffolds.

Published version
Peer-reviewed

Type

Article

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Authors

Hume, Robert D 
Pensa, Sara 
Brown, Elizabeth J 
Hitchcock, Jessica 

Abstract

Breast cancers are highly heterogeneous and their metastatic potential and response to therapeutic drugs is difficult to predict. A tool that could accurately gauge tumour invasiveness and drug response would provide a valuable addition to the oncologist's arsenal. We have developed a 3-dimensional (3D) culture model that recapitulates the stromal environment of breast cancers by generating anisotropic (directional) collagen scaffolds seeded with adipocytes and culturing tumour fragments therein. Analysis of tumour cell invasion in the presence of various therapeutic drugs, by immunofluorescence microscopy coupled with an optical clearing technique, demonstrated the utility of this approach in determining both the rate and capacity of tumour cells to migrate through the stroma while shedding light also on the mode of migration. Furthermore, the response of different murine mammary tumour types to chemotherapeutic drugs could be readily quantified.

Description

Keywords

3T3-L1 Cells, Adipocytes, Animals, Cell Movement, Collagen, Female, Humans, Immunohistochemistry, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Microscopy, Fluorescence, Tissue Engineering, Tissue Scaffolds

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/K011014/1)
European Research Council (320598)
Medical Research Council (MR/N022963/1)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/K001655/1)