Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment

• Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Breast cancer

Cancer stem cells

Differentiation

Infiltration

Malignancy

Scaffold

Cell culture

Cell proliferation

Differentiation (calculus)

Diseases

Gene expression

Mass spectrometry

Scaffolds

Stem cells

Tumors

Epithelial-mesenchymal transition

Experimental platform

Gene expression profiling

Mass spectrometry analysis

Tumor microenvironment

Scaffolds (biology)

Breast cancer

Cancer stem cells

Differentiation

Infiltration

Malignancy

Scaffold

tumor xenografts

tissue scaffold

in-vitro

stem

expression

models

cells

hallmarks

culture

3rd-dimension

Engineering

Materials Science

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