Research report: POSTN+ tumor-associated endothelial cells promote and predict pulmonary metastasis in osteosarcoma

In a study published in Cellular Oncology, researchers report that endothelial cells expressing the protein periostin, or POSTN, appear to actively promote pulmonary metastasis and can serve as a predictive marker for which patients are at highest risk.

Pulmonary metastasis remains the leading cause of death in osteosarcoma, even as surgery and chemotherapy have improved overall survival. Whether lung lesions appear at diagnosis or later, metastatic disease is the central clinical challenge, and the mechanisms that enable tumor cells to seed the lung have remained incompletely understood.

To probe those mechanisms, the team integrated single-cell RNA sequencing data to compare the tumor microenvironment of metastatic and non-metastatic osteosarcoma, focusing on the role of endothelial cells. This analysis revealed a previously unrecognized subset of tumor-associated endothelial cells, or TECs, characterized by POSTN expression, that the authors describe as critical for driving pulmonary metastasis.

The findings were not left resting on a single dataset. The researchers validated their results through independent single-cell RNA sequencing analysis and Western blotting in four samples, a real-world clinical cohort of 49 patients, and the TCGA dataset covering 91 cases. An integrated multi-omics approach was then used to delineate how these cells function mechanistically.

Clinical validation showed that high infiltration of POSTN-positive TECs serves as an independent predictor of pulmonary metastasis and of reduced metastasis-free survival. In other words, the density of these specialized blood-vessel cells within a tumor appears to carry prognostic information beyond established clinical factors.

The mechanistic story is one of dual pathways. According to the study, POSTN binds to the integrin ITGB3 on osteoclasts, activating FAK-PI3K/AKT signaling that drives degradation of bone matrix. At the same time, POSTN-positive TECs recruit and activate regulatory T cells, or Tregs, establishing an immunosuppressive niche that may shield disseminating tumor cells from immune attack.

This combination of bone destruction and immune suppression offers a coherent account of how the metastatic process is supported from within the tumor microenvironment.

The authors conclude that POSTN-positive TECs are key drivers of osteosarcoma pulmonary metastasis, serving both as a robust predictive biomarker and as a promising therapeutic target. The authors state that POSTN-positive TECs represent a promising therapeutic target, though this remains a proposed direction rather than a demonstrated treatment effect.

As with any early-release study, the work is peer-reviewed and citable but subject to further edits before the final version of record. The clinical cohorts are modest in size, and the mechanistic pathways will require further testing in experimental and clinical settings.

Subject of Research: The role of POSTN-positive tumor-associated endothelial cells in promoting and predicting pulmonary metastasis in osteosarcoma.

Article Title: POSTN+ tumor-associated endothelial cells promote and predict pulmonary metastasis in osteosarcoma

Article References: Ji, C., Chen, G., Liu, H., Miao, X., Ding, S., Zhang, X., Wang, F., Wang, D., Li, M., Zhang, H.-M., Li, J., & Lu, Y. (2026). POSTN+ tumor-associated endothelial cells promote and predict pulmonary metastasis in osteosarcoma. Cellular Oncology. https://doi.org/10.1007/s13402-026-01306-2

Image Credits: AI Generated

DOI: 10.1007/s13402-026-01306-2

Keywords: osteosarcoma, pulmonary metastasis, tumor-associated endothelial cells, periostin, single-cell RNA sequencing, tumor microenvironment, biomarker, Tregs, ITGB3, FAK-PI3K/AKT signaling, metastasis-free survival, Cellular Oncology