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Specific Enhanced Expression of Platelet-Derived Endothelial Cell Growth Factor in Submucosa of Human Colorectal Cancer

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

PURPOSE

Platelet-derived endothelial cell growth factor, identified to be an angiogenic factor, has been implicated in metastases of colorectal cancer. This study aimed to clarify the role and localization of platelet-derived endothelial cell growth factor associated with human colorectal cancer invasion.

METHODS

Thirty-two patients with colorectal cancer who had undergone surgery were analyzed. Platelet-derived endothelial cell growth factor enzyme activities in the colorectal cancer specimens were measured. Cells that expressed platelet-derived endothelial cell growth factor were identified and localized by immunohistochemical analysis with anti-human platelet-derived endothelial cell growth factor antibody and by in situ hybridization with specific RNA probe.

RESULTS

Platelet-derived endothelial cell growth factor enzyme activity increased significantly in cancer tissues compared with normal colonic mucosa at various distances from the cancer. Immunohistochemical analysis and in situ hybridization demonstrated platelet-derived endothelial cell growth factor expression in stromal macrophages and fibroblasts located in cancer tissues and surrounding noncancerous tissues, although the tumor cells and normal colonic mucosa were negative. The value of platelet-derived endothelial cell growth factor expression was highest at the border of the colorectal cancer (35.3 ± 8.9 percent), followed by the cancer nest (15.2 ± 9.2 percent) and normal mucosa (7.7 ± 3.4 percent). In the border area, the highest value of platelet-derived endothelial cell growth factor expression was observed in the submucosa (35.3 ± 8.9 percent), followed by the muscular propria (21.9 ± 7.7 percent) and the subserosa (14.9 ± 5.5 percent).

CONCLUSIONS

Stromal macrophages and fibroblasts are responsible for elevated platelet-derived endothelial cell growth factor activity in colorectal cancer. The significance of enhanced expression of platelet-derived endothelial cell growth factor in the submucosa at the cancer border remains unclear. Cancer stroma may be an important factor for cancer angiogenesis and may serve as a treatment target through specific modulation of angiogenic factors.

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ACKNOWLEDGMENTS

The authors thank Dr. Nobuyuki Kobayashi (Department of Surgery, Kitasato University) for his kind advice during this study.

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Authors and Affiliations

  1. Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan

    Tadashi Nozawa M.D., Takumo Enomoto M.D., Yoshitomo Koshida M.D. & Masaru Kuranami M.D.

  2. Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Japan

    Yuichi Sato Ph.D.

Authors
  1. Tadashi Nozawa M.D.
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  2. Takumo Enomoto M.D.
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  3. Yoshitomo Koshida M.D.
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  4. Yuichi Sato Ph.D.
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  5. Masaru Kuranami M.D.
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Correspondence to Masaru Kuranami M.D..

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Nozawa, T., Enomoto, T., Koshida, Y. et al. Specific Enhanced Expression of Platelet-Derived Endothelial Cell Growth Factor in Submucosa of Human Colorectal Cancer. Dis Colon Rectum 47, 2093–2100 (2004). https://doi.org/10.1007/s10350-004-0712-y

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  • DOI: https://doi.org/10.1007/s10350-004-0712-y

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