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The Hypoxic Environment in Tumor-Stromal Cells Accelerates Pancreatic Cancer Progression via the Activation of Paracrine Hepatocyte Growth Factor/c-Met Signaling

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

Abstract

Background

Pancreatic cancer is one of the representative solid tumors, in which the hypoxic microenvironment plays a crucial role in malignant progression. We previously demonstrated that tumor-stromal interaction under hypoxia enhances the invasiveness of pancreatic cancer cells through hepatocyte growth factor (HGF)/c-Met signaling.

Methods

We investigated the immunohistochemical expression of hypoxia inducible factor-1α (HIF-1α) c-Met, and HGF in both cancer and stromal cells using 41 pancreatic cancer tissue specimens, and tried to identify any correlations with the clinical features and survival.

Results

Positive staining for HIF-1α was observed in both pancreatic cancer and the surrounding stromal cells in more than 30% of the cases, and it significantly correlated with lymph node metastasis (P < .05). A significant correlation was observed between the expression of HIF-1α and HGF in stromal cells (P < .05). In addition, the c-Met expression in cancer cells was found to significantly correlate with the HGF expression in not only cancer but also stromal cells. The disease-free survival rates of the patients with HIF-1α in cancer, stromal, c-Met in cancer, and an HGF expression in stromal cells was significantly worse than those without such expressions (P < .05).

Conclusions

These data suggest that the HGF/c-Met signaling via HIF-1α ?may therefore negatively affect the prognosis in patients with pancreatic cancer, and targeting tumor stroma under hypoxia might thus be potentially useful as a novel therapy for this cancer.

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Acknowledgment

We thank Dr. D. Mori and K. Kai for the advice on immunohistochemical analysis.

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Authors and Affiliations

  1. Department of Surgery, Saga University Faculty of Medicine, Saga, Japan

    Takao Ide, Yoshihiko Kitajima, Atsushi Miyoshi, Takao Ohtsuka, Mayumi Mitsuno, Kazuma Ohtaka & Kohji Miyazaki

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  1. Takao Ide
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  2. Yoshihiko Kitajima
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  3. Atsushi Miyoshi
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  4. Takao Ohtsuka
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  5. Mayumi Mitsuno
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  6. Kazuma Ohtaka
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  7. Kohji Miyazaki
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Correspondence to Kohji Miyazaki.

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Ide, T., Kitajima, Y., Miyoshi, A. et al. The Hypoxic Environment in Tumor-Stromal Cells Accelerates Pancreatic Cancer Progression via the Activation of Paracrine Hepatocyte Growth Factor/c-Met Signaling. Ann Surg Oncol 14, 2600–2607 (2007). https://doi.org/10.1245/s10434-007-9435-3

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  • DOI: https://doi.org/10.1245/s10434-007-9435-3

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