Junko Tsuchida1, Masayuki Nagahashi2, Masato Nakajima1, Kazuki Moro1, Kumiko Tatsuda1, Rajesh Ramanathan3, Kazuaki Takabe4, Toshifumi Wakai1. 1. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. 2. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. Electronic address: mnagahashi@med.niigata-u.ac.jp. 3. Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia. 4. Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia; Breast Surgery, Roswell Park Cancer Institute, Buffalo, New York.
Abstract
BACKGROUND: Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis, and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis. However, the associations between S1P and clinical parameters in human breast cancer have not been well investigated to date. MATERIALS AND METHODS: We determined levels of S1P and other sphingolipids in breast cancer tissue by electrospray ionization-tandem mass spectrometry. Associations between S1P levels and clinicopathologic features of the tumors were analyzed. Expression of phospho-SphK1 (pSphK1) in breast cancer tissues was determined by immunohistochemical scoring. RESULTS: Levels of S1P in breast cancer tissues were significantly higher in patients with high white blood cell count in the blood than those patients without. S1P levels were lower in patients with human epidermal growth factor receptor 2 overexpression and/or amplification than those patients without. Furthermore, cancer tissues with high pSphK1 expression showed significantly higher levels of S1P than cancer tissues without. Finally, patients with lymph node metastasis showed significantly higher levels of S1P in tumor tissues than the patients with negative nodes. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn is associated with lymphatic metastasis in breast cancer.
BACKGROUND:Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis, and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis. However, the associations between S1P and clinical parameters in humanbreast cancer have not been well investigated to date. MATERIALS AND METHODS: We determined levels of S1P and other sphingolipids in breast cancer tissue by electrospray ionization-tandem mass spectrometry. Associations between S1P levels and clinicopathologic features of the tumors were analyzed. Expression of phospho-SphK1 (pSphK1) in breast cancer tissues was determined by immunohistochemical scoring. RESULTS: Levels of S1P in breast cancer tissues were significantly higher in patients with high white blood cell count in the blood than those patients without. S1P levels were lower in patients with human epidermal growth factor receptor 2 overexpression and/or amplification than those patients without. Furthermore, cancer tissues with high pSphK1 expression showed significantly higher levels of S1P than cancer tissues without. Finally, patients with lymph node metastasis showed significantly higher levels of S1P in tumor tissues than the patients with negative nodes. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn is associated with lymphatic metastasis in breast cancer.
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