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Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer.
Horino, Taichi; Horiguchi, Haruki; Yumoto, Shinsei; Kadomatsu, Tsuyoshi; Hara, Yoshihiro; Yagi, Taisuke; Baba, Yoshifumi; Miyamoto, Yuji; Baba, Hideo; Oike, Yuichi.
Afiliação
  • Horino T; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
  • Horiguchi H; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Yumoto S; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. horiguti@kumamoto-u.ac.jp.
  • Kadomatsu T; Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. horiguti@kumamoto-u.ac.jp.
  • Hara Y; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
  • Yagi T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Baba Y; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
  • Miyamoto Y; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Baba H; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Oike Y; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Ann Surg Oncol ; 31(12): 7693-7704, 2024 Nov.
Article em En | MEDLINE | ID: mdl-38981990
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)-ß, 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Biomarcadores Tumorais / Progressão da Doença / Microambiente Tumoral / Proteínas Semelhantes a Angiopoietina / Macrófagos Associados a Tumor / Proteína 2 Semelhante a Angiopoietina Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Biomarcadores Tumorais / Progressão da Doença / Microambiente Tumoral / Proteínas Semelhantes a Angiopoietina / Macrófagos Associados a Tumor / Proteína 2 Semelhante a Angiopoietina Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão