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

脂肪细胞植入的 3D 工程各向异性胶原支架中的肿瘤细胞侵袭性和对化疗的反应

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作者:Robert D Hume, Sara Pensa, Elizabeth J Brown, Peter A Kreuzaler, Jessica Hitchcock, Anke Husmann, Jonathan J Campbell, Annabel O Lloyd-Thomas, Ruth E Cameron, Christine J Watson

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.

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