IngentaConnect The Hypoxic Environment in Tumor-Stromal Cells Accelerates Pancre...

Authors: Ide, Takao; Kitajima, Yoshihiko; Miyoshi, Atsushi; Ohtsuka, Takao; Mitsuno, Mayumi; Ohtaka, Kazuma; Miyazaki, Kohji¹

Source: Annals of Surgical Oncology, Volume 14, Number 9, September 2007 , pp. 2600-2607(8)

Publisher: Springer

Abstract:

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.

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.

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).

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.

Keywords: Pancreatic cancer; Hypoxia; Tumor-stromal interaction; Hepatocyte growth factor; c-Met

Document Type: Research article

DOI: 10.1245/s10434-007-9435-3

Affiliations: 1: Email: miyazak2@cc.saga-u.ac.jp

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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