Erschienen in:

09.07.2024 | Translational Research

Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer

verfasst von: Taichi Horino, MD, Haruki Horiguchi, PhD, Shinsei Yumoto, MD, Tsuyoshi Kadomatsu, PhD, Yoshihiro Hara, MD, Taisuke Yagi, MD, PhD, Yoshifumi Baba, MD, PhD, Yuji Miyamoto, MD, PhD, Hideo Baba, MD, PhD, Yuichi Oike, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 12/2024

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Abstract

Background

Tumor-associated macrophages (TAM), a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts.

Methods

We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database.

Results

In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-β, a TAM-activating factor, in esophageal cancer cell lines.

Conclusion

We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression.

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Titel: Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer
verfasst von: Taichi Horino, MD
Haruki Horiguchi, PhD
Shinsei Yumoto, MD
Tsuyoshi Kadomatsu, PhD
Yoshihiro Hara, MD
Taisuke Yagi, MD, PhD
Yoshifumi Baba, MD, PhD
Yuji Miyamoto, MD, PhD
Hideo Baba, MD, PhD
Yuichi Oike, MD, PhD
Publikationsdatum: 09.07.2024
Verlag: Springer International Publishing
Erschienen in: Annals of Surgical Oncology / Ausgabe 12/2024
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-024-15557-6

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Springer Medizin

Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer

Abstract

Background

Methods

Results

Conclusion

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