ArticleClinical and translational medicine2021
The multicellular signalling network of ovarian cancer metastases.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- A pro-inflammatory metastasis-associated macrophage subset induces tumor-promoting mesothelial cell conversion in ovarian cancer via IL-1α secretion.Cell death & disease · 2026Article
- Tumor-associated macrophages display differential protein cargo sorting in extracellular vesicles associated with poor survival in ovarian cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Immune heterogeneity and therapeutic resistance in gynecological malignancies.Frontiers in immunology · 2026Review
- Basal cell adhesion molecule (BCAM) promotes mesothelial-to-mesenchymal transition and tumor angiogenesis through paracrine signaling.Cell communication and signaling : CCS · 2025Article
- Pregnancy is associated with the prognosis of ovarian cancer patients with abdominal metastasis.American journal of cancer research · 2025Article
- Processed Products ofAnti-cancer agents in medicinal chemistry · 2025Article
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- Exosomal ANXA2 facilitates ovarian cancer peritoneal metastasis by activating peritoneal mesothelial cells through binding with TLR2.Cell communication and signaling : CCS · 2024Article
- Arachidonic acid impairs natural killer cell functions by disrupting signaling pathways driven by activating receptors and reactive oxygen species.Cell communication and signaling : CCS · 2024Article
- Reciprocal crosstalk between Th17 and mesothelial cells promotes metastasis-associated adhesion of ovarian cancer cells.Clinical and translational medicine · 2024Article
- Implication of fibroblast growth factor 7 in ovarian cancer metastases and patient survival.Frontiers in oncology · 2024Article
- TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion.iScience · 2023Article
- Endoplasmic Reticulum Stress-Related Ten-Biomarker Risk Classifier for Survival Evaluation in Epithelial Ovarian Cancer andInternational journal of molecular sciences · 2023Article
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.Frontiers in immunology · 2023Article
- Cancer-associated fibroblasts in gynecological malignancies: are they really allies of the enemy?Frontiers in oncology · 2023Review
- The lysophosphatidic acid-regulated signal transduction network in ovarian cancer cells and its role in actomyosin dynamics, cell migration and entosis.Theranostics · 2023Article
- Basal cell adhesion molecule promotes metastasis-associated processes in ovarian cancer.Clinical and translational medicine · 2023Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTranscoelomic spread is the major route of metastasis of ovarian high-grade serous carcinoma (HGSC) with the omentum as the major metastatic site. Its unique tumour microenvironment with its large populations of adipocytes, mesothelial cells and immune cells establishes an intercellular signaling network that is instrumental for metastatic growth yet poorly understood.
methodsBased on transcriptomic analysis of tumour cells, tumour-associated immune and stroma cells we defined intercellular signaling pathways for 284 cytokines and growth factors and their cognate receptors after bioinformatic adjustment for contaminating cell types. The significance of individual components of this network was validated by analysing clinical correlations and potentially pro-metastatic functions, including tumour cell migration, pro-inflammatory signal transduction and TAM expansion.
resultsThe data show an unexpected prominent role of host cells, and in particular of omental adipocytes, mesothelial cells and fibroblasts (CAF), in sustaining this signaling network. These cells, rather than tumour cells, are the major source of most cytokines and growth factors in the omental microenvironment (n = 176 vs. n = 13). Many of these factors target tumour cells, are linked to metastasis and are associated with a short survival. Likewise, tumour stroma cells play a major role in extracellular-matrix-triggered signaling. We have verified the functional significance of our observations for three exemplary instances. We show that the omental microenvironment (i) stimulates tumour cell migration and adhesion via WNT4 which is highly expressed by CAF; (ii) induces pro-tumourigenic TAM proliferation in conjunction with high CSF1 expression by omental stroma cells and (iii) triggers pro-inflammatory signaling, at least in part via a HSP70-NF-κB pathway.
conclusionsThe intercellular signaling network of omental metastases is majorly dependent on factors secreted by immune and stroma cells to provide an environment that supports ovarian HGSC progression. Clinically relevant pathways within this network represent novel options for therapeutic intervention.
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