Cancer‐associated fibroblast heterogeneity in chordoma†

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Main Authors: Jack C Henry, Angus J M Cameron
Format: Artículo Open Access
Published: Wiley 2025
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author Jack C Henry
Angus J M Cameron
author_facet Jack C Henry
Angus J M Cameron
Jack C Henry
Angus J M Cameron
collection Wiley Open Access
contents Cancer‐associated fibroblast heterogeneity in chordoma† Jack C Henry Angus J M Cameron The Journal of Pathology AbstractIn solid tumours, malignant cells develop relationships with nonmalignant stromal cells to support tumour growth, tissue structure, and nutrient supply. In a recent issue of this journal, Zheng and Guo catalogue the cellular landscape in chordoma using a combination of single‐cell and spatial transcriptomics. Despite the mesenchymal nature of chordoma, malignant cells retain expression of epithelial markers, in addition to mesenchymal, partial‐EMT, and stem‐cell signatures. Cancer‐associated fibroblasts (CAFs) are among the most abundant stromal cells and the authors define an inflammatory CAF subtype (iCAF), which is associated with poor outcome and tumour invasion. It is proposed that iCAFs arise from normal fibroblasts during malignant tumour progression and play a causative role in driving an invasive poor prognosis tumour phenotype. Recent reports by this and other groups have separately catalogued cell populations, including CAFs and immune cells in chordoma. The next challenge will be to integrate findings from these distinct studies to allow a consensus to be reached regarding cellular heterogeneity within chordoma, and to allow comparison of CAF populations with those found in other tumour types. Comparison of CAF functions in these predominantly mesenchymal tumours with epithelial solid tumours may reveal interesting lessons about the diverse phenotypes CAFs can bring to distinct tumour ecosystems. Understanding the role of CAFs in chordoma progression may also lead to therapeutic opportunities, but separation of correlation and causation in CAF regulation of tumour phenotypes remains a significant challenge. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6420 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1002/path.6420
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institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2025
publisher Wiley
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spellingShingle Cancer‐associated fibroblast heterogeneity in chordoma†
Jack C Henry
Angus J M Cameron
The Journal of Pathology
Cancer‐associated fibroblast heterogeneity in chordoma† Jack C Henry Angus J M Cameron The Journal of Pathology AbstractIn solid tumours, malignant cells develop relationships with nonmalignant stromal cells to support tumour growth, tissue structure, and nutrient supply. In a recent issue of this journal, Zheng and Guo catalogue the cellular landscape in chordoma using a combination of single‐cell and spatial transcriptomics. Despite the mesenchymal nature of chordoma, malignant cells retain expression of epithelial markers, in addition to mesenchymal, partial‐EMT, and stem‐cell signatures. Cancer‐associated fibroblasts (CAFs) are among the most abundant stromal cells and the authors define an inflammatory CAF subtype (iCAF), which is associated with poor outcome and tumour invasion. It is proposed that iCAFs arise from normal fibroblasts during malignant tumour progression and play a causative role in driving an invasive poor prognosis tumour phenotype. Recent reports by this and other groups have separately catalogued cell populations, including CAFs and immune cells in chordoma. The next challenge will be to integrate findings from these distinct studies to allow a consensus to be reached regarding cellular heterogeneity within chordoma, and to allow comparison of CAF populations with those found in other tumour types. Comparison of CAF functions in these predominantly mesenchymal tumours with epithelial solid tumours may reveal interesting lessons about the diverse phenotypes CAFs can bring to distinct tumour ecosystems. Understanding the role of CAFs in chordoma progression may also lead to therapeutic opportunities, but separation of correlation and causation in CAF regulation of tumour phenotypes remains a significant challenge. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6420 http://creativecommons.org/licenses/by/4.0/
title Cancer‐associated fibroblast heterogeneity in chordoma†
topic The Journal of Pathology
url https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6420