Abstract
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.
Highlights
Cancer is one of the leading causes of death worldwide and both incidence and mortality is increasing [1]
To gain more information about the cellular profile of individual cells, we examined the possibility of combining several types of gene expression analyses in a flexible manner
The targeted approach instead uses a combination of oligodT primers and random hexamers during reverse transcription, followed by preamplification using multiplex PCR with a pool of primers targeting a predefined panel of genes (Figure 6)
Summary
Cancer is one of the leading causes of death worldwide and both incidence and mortality is increasing [1]. The main treatments of cancer include surgery to remove the tumor, radiotherapy directed at the tumor site and chemotherapy; cytotoxic drugs that aims to kill highly proliferative cancer cells while causing little harm to normal cells. As our knowledge about altered signaling pathways has increased, new possibilities for development of directed treatments have increased though with varying results [2, 4]. Both prognosis and treatment response commonly varies between patients with the same cancer type and there are several issues associated with today’s treatments. Increased knowledge about tumor cell heterogeneity could be the key to understanding the difference in treatment response between patients and to design new and more efficient treatments
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