Sphingosine-1-Phosphate-Triggered Expression of Cathelicidin LL-37 Promotes the Growth of Human Bladder Cancer Cells.
Tomasz Wollny, Urszula Wnorowska, Ewelina Piktel, ��ukasz Suprewicz, Grzegorz Kr��l, Katarzyna G��uszek, Stanis��aw G����d��, Janusz Kopczy��ski, Robert Bucki
Author Information
Tomasz Wollny: Holy Cross Oncology Center of Kielce, Artwi��skiego 3, 25-734 Kielce, Poland. ORCID
Urszula Wnorowska: Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland.
Ewelina Piktel: Independent Laboratory of Nanomedicine, Medical University of Bialystok, Mickiewicza 2B, 15-222 Bialystok, Poland.
��ukasz Suprewicz: Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland. ORCID
Grzegorz Kr��l: Department of Microbiology and Immunology, Institute of Medical Science, Collegium Medicum, Jan Kochanowski University of Kielce, IX Wiek��w Kielc 19A, 25-317 Kielce, Poland.
Katarzyna G��uszek: Holy Cross Oncology Center of Kielce, Artwi��skiego 3, 25-734 Kielce, Poland.
Stanis��aw G����d��: Holy Cross Oncology Center of Kielce, Artwi��skiego 3, 25-734 Kielce, Poland.
Janusz Kopczy��ski: Holy Cross Oncology Center of Kielce, Artwi��skiego 3, 25-734 Kielce, Poland.
Robert Bucki: Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland. ORCID
It has been proven that tumour growth and progression are regulated by a variety of mediators released during the inflammatory process preceding the tumour appearance, but the role of inflammation in the development of bladder cancer is ambiguous. This study was designed around the hypothesis that sphingosine-1-phosphate (S1P), as a regulator of several cellular processes important in both inflammation and cancer development, may exert some of the pro-tumorigenic effects indirectly due to its ability to regulate the expression of human cathelicidin (hCAP-18). LL-37 peptide released from hCAP-18 is involved in the development of various types of cancer in humans, especially those associated with infections. Using immunohistological staining, we showed high expression of hCAP-18/LL-37 and sphingosine kinase 1 (the enzyme that forms S1P from sphingosine) in human bladder cancer cells. In a cell culture model, S1P was able to stimulate the expression and release of hCAP-18/LL-37 from human bladder cells, and the addition of LL-37 peptide dose-dependently increased their proliferation. Additionally, the effect of S1P on LL-37 release was inhibited in the presence of FTY720P, a synthetic immunosuppressant that blocks S1P receptors. Together, this study presents the possibility of paracrine relation in which LL-37 production following cell stimulation by S1P promotes the development and growth of bladder cancer.
