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Clinical Significance of Folate Receptor β–expressing Tumor-associated Macrophages in Pancreatic Cancer

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To examine the appearance and distribution of folate receptor β-expressing (FRβ+) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients.

Methods

Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FRβ+ and tumor-infiltrating (CD68+) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FRβ monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FRβ-expressing or CD68+ macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68+ or FRβ+ macrophages, clinicopathologic factors, and overall survival.

Results

FRβ+ macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68+ macrophages. A high number of FRβ+ macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients.

Conclusions

FRβ+ macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRβ+ macrophages may be promising a targeting therapy for pancreatic cancer.

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Acknowledgment

Supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Ministry of Health, Labour, and Welfare, Japan.

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Authors and Affiliations

  1. Department of Digestive Surgery, Kagoshima University, Kagoshima, Japan

    Hiroshi Kurahara MD, PhD, Taisaku Kuwahata MD, Koki Maeda MD, Yuko Mataki MD, PhD, Kosei Maemura MD, PhD & Shoji Natsugoe MD, PhD

  2. Department of Cancer and Regenerative Medicine, Kagoshima University, Kagoshima, Japan

    Sonshin Takao MD, PhD

  3. Frontier Science Research Center, Kagoshima University, Kagoshima, Japan

    Sonshin Takao MD, PhD, Taisaku Kuwahata MD, Qiang Ding MD, PhD & Koki Maeda MD

  4. Department of Immunology, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan

    Taku Nagai PhD & Takami Matsuyama MD, PhD

  5. Department of Health Sciences, Kagoshima University, Kagoshima, Japan

    Hiroyuki Shinchi MD, PhD

Authors
  1. Hiroshi Kurahara MD, PhD
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  2. Sonshin Takao MD, PhD
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  3. Taisaku Kuwahata MD
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  4. Taku Nagai PhD
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  5. Qiang Ding MD, PhD
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  6. Koki Maeda MD
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  7. Hiroyuki Shinchi MD, PhD
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  8. Yuko Mataki MD, PhD
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  9. Kosei Maemura MD, PhD
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  10. Takami Matsuyama MD, PhD
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  11. Shoji Natsugoe MD, PhD
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Corresponding author

Correspondence to Sonshin Takao MD, PhD.

Additional information

Hiroshi Kurahara and Sonshin Takao contributed equally to this work.

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Kurahara, H., Takao, S., Kuwahata, T. et al. Clinical Significance of Folate Receptor β–expressing Tumor-associated Macrophages in Pancreatic Cancer. Ann Surg Oncol 19, 2264–2271 (2012). https://doi.org/10.1245/s10434-012-2263-0

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  • DOI: https://doi.org/10.1245/s10434-012-2263-0

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