ArticleCell communication and signaling : CCS2021
Patient-derived scaffolds influence secretion profiles in cancer cells mirroring clinical features and breast cancer subtypes.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 15 citations in OpenAlex.
- A systemic immune signature stratifies early-stage breast cancer patients and reveals soluble IL-2RA and PD-1 as potential independent prognostic biomarkers.Breast cancer research : BCR · 2026Article
- Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features.Journal of translational medicine · 2023Article
- Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.Cancers · 2023Article
- Research trends and prospects on brain metastasis from breast cancer: A bibliometric analysis.Frontiers in oncology · 2023Article
- The Hepatic Pre-Metastatic Niche.Cancers · 2022Review
- Combined Application of Patient-Derived Cells and Biomaterials as 3D In Vitro Tumor Models.Cancers · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBreast cancer is a common malignancy with varying clinical behaviors and for the more aggressive subtypes, novel and more efficient therapeutic approaches are needed. Qualities of the tumor microenvironment as well as cancer cell secretion have independently been associated with malignant clinical behaviors and a better understanding of the interplay between these two features could potentially reveal novel targetable key events linked to cancer progression.
methodsA newly developed human derived in vivo-like growth system, consisting of decellularized patient-derived scaffolds (PDSs) recellularized with standardized breast cancer cell lines (MCF7 and MDA-MB-231), were used to analyze how 63 individual patient specific microenvironments influenced secretion determined by proximity extension assays including 184 proteins and how these relate to clinical outcome.
resultsThe secretome from cancer cells in PDS cultures varied distinctly from cells grown as standard monolayers and besides a general increase in secretion from PDS cultures, several secreted proteins were only detectable in PDSs. Monolayer cells treated with conditioned media from PDS cultures, further showed increased mammosphere formation demonstrating a cancer stem cell activating function of the PDS culture induced secretion. The detailed secretomic profiles from MCF7s growing on 57 individual PDSs differed markedly but unsupervised clustering generated three separate groups having similar secretion profiles that significantly correlated to different clinical behaviors. The secretomic profile that associated with cancer relapse and high grade breast cancer showed induced secretion of the proteins IL-6, CCL2 and PAI-1, all linked to cancer stem cell activation, metastasis and priming of the pre-metastatic niche. Cancer promoting pathways such as "Suppress tumor immunity" and "Vascular and tissue remodeling" was also linked to this more malignant secretion cluster.
conclusionPDSs repopulated with cancer cells can be used to assess how cancer secretion is effected by specific and varying microenvironments. More malignant secretion patterns induced by specific patient based cancer microenvironments could further be identified pinpointing novel therapeutic opportunities targeting micro environmentally induced cancer progression via secretion of potent cytokines. Video abstract.
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