Single-cell RNA-seq reveals SPP1⁺ tumor-associated macrophage population associated with collagen remodeling in anaplastic thyroid cancer.
- 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, China.
- 2Department of Chemistry, National University of Singapore, Singapore, 117557, Singapore.
- 3Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, China. [email protected].
Abstract
Background
Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal malignancies. ATC tumor cells exhibit marked overexpression of collagen family genes; however, the mechanisms underlying tumor cell-driven collagen remodeling remain poorly understood. Tumor-associated macrophages (TAMs) constitute a substantial proportion of the ATC tumor microenvironment, yet whether and how TAMs influence collagen remodeling in ATC tumor cells remains unclear.Methods
We combined single-cell RNA sequencing and bulk transcriptomic data from public databases to explore the role of TAMs in collagen remodeling of tumor cells in ATC. Additionally, in vivo mouse tumor models were employed to assess tumor growth, followed by immunofluorescence analysis of tumor tissues.Results
Single-cell transcriptomic analyses revealed pronounced myeloid enrichment and a dominant mesenchymal-like malignant epithelial state in ATC. This population exhibited a collagen-high transcriptional program associated with increased collagen deposition and unfavorable outcomes in the broader thyroid carcinoma context. CIBERSORTx-based deconvolution of multiple bulk RNA-seq cohorts independently confirmed expansion of myeloid cells in ATC and a positive correlation between tumor and myeloid proportions. Further characterization identified an ATC-enriched SPP1⁺ TAMs subset with strong extracellular matrix remodeling signatures. Cell-cell communication and spatial inference analyses highlighted SPP1-CD44 signaling as a predicted interaction between SPP1⁺ TAMs and mesenchymal ATC cells. In vivo inhibition of SPP1 partially restrained tumor growth and collagen accumulation. Pseudotime analysis further suggested VSIG4⁺ TAMs as an upstream state associated with SPP1⁺ TAM emergence.Conclusions
Targeting the SPP1 axis may disrupt macrophage-driven collagen remodeling and offer new therapeutic opportunities for ATC.
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BibTeX
@article{yu2026singlecell,
title = {{Single-cell RNA-seq reveals SPP1⁺ tumor-associated macrophage population associated with collagen remodeling in anaplastic thyroid cancer.}},
author = {Dingyi Yu and Kaiyu Jin and Shu Sun and Mengyu Chen and Xiaofen Yi and Lu Chen},
journal = {BMC cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16648-1},
url = {https://europepmc.org/article/MED/42963735},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Single-cell RNA-seq reveals SPP1⁺ tumor-associated macrophage population associated with collagen remodeling in anaplastic thyroid cancer.
AU - Dingyi Yu
AU - Kaiyu Jin
AU - Shu Sun
AU - Mengyu Chen
AU - Xiaofen Yi
AU - Lu Chen
PY - 2026
DA - 2026/08/01
JO - BMC cancer
DO - 10.1186/s12885-026-16648-1
UR - https://europepmc.org/article/MED/42963735
AB - Background Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal malignancies. ATC tumor cells exhibit marked overexpression of collagen family genes; however, the mechanisms underlying tumor cell-driven collagen remodeling remain poorly understood. Tumor-associated macrophages (TAMs) constitute a substantial proportion of the ATC tumor microenvironment, yet whether and how TAMs influence collagen remodeling in ATC tumor cells remains unclear.Methods We combined single-cell RNA sequencing and bulk transcriptomic data from public databases to explore the role of TAMs in collagen remodeling of tumor cells in ATC. Additionally, in vivo mouse tumor models were employed to assess tumor growth, followed by immunofluorescence analysis of tumor tissues.Results Single-cell transcriptomic analyses revealed pronounced myeloid enrichment and a dominant mesenchymal-like malignant epithelial state in ATC. This population exhibited a collagen-high transcriptional program associated with increased collagen deposition and unfavorable outcomes in the broader thyroid carcinoma context. CIBERSORTx-based deconvolution of multiple bulk RNA-seq cohorts independently confirmed expansion of myeloid cells in ATC and a positive correlation between tumor and myeloid proportions. Further characterization identified an ATC-enriched SPP1⁺ TAMs subset with strong extracellular matrix remodeling signatures. Cell-cell communication and spatial inference analyses highlighted SPP1-CD44 signaling as a predicted interaction between SPP1⁺ TAMs and mesenchymal ATC cells. In vivo inhibition of SPP1 partially restrained tumor growth and collagen accumulation. Pseudotime analysis further suggested VSIG4⁺ TAMs as an upstream state associated with SPP1⁺ TAM emergence.Conclusions Targeting the SPP1 axis may disrupt macrophage-driven collagen remodeling and offer new therapeutic opportunities for ATC.
SN - 1471-2407
ER -