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Review

The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma

Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
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Academic Editors: Srikumar Chellappan and Jaya Padmanabhan
Int. J. Mol. Sci. 2017, 18(3), 600; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18030600
Received: 30 January 2017 / Revised: 4 March 2017 / Accepted: 6 March 2017 / Published: 9 March 2017
(This article belongs to the Special Issue Pancreatic Disorders)
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases to affect humans, regardless of whether patients receive multimodal therapy (including surgery, radiotherapy, and chemotherapy). This resistance to intervention is currently considered to be caused by the desmoplastic change of the extracellular matrix (ECM) in PDAC tissues, which is characterized by the accumulation of cancer-associated fibroblasts, collagen, proteoglycan, and hyaluronan. Among these ECM components, hyaluronan has attracted interest because various studies have indicated that hyaluronan-rich PDAC is correlated with the progressive properties of cancer cells, both in experimental and clinical settings. Hence, the reduction of hyaluronan in cancer tissue may represent a novel therapeutic approach for PDAC. 4-methylumbelliferone (4-MU) is a derivative of coumarin that was reported to suppress the synthesis of hyaluronan in cultured human skin fibroblasts in 1995. As an additional study, our group firstly reported that 4-MU reduced the hyaluronan synthesis of mouse melanoma cells and exerted anti-cancer activity. Subsequently, we have showed that 4-MU inhibited liver metastasis in mice inoculated with human pancreatic cancer cells. Thereafter, 4-MU has been accepted as an effective agent for hyaluronan research and is expected to have clinical applications. This review provides an overview of the interaction between PDAC and hyaluronan, the properties of 4-MU as a suppressor of the synthesis of hyaluronan, and the perspectives of PDAC treatment targeting hyaluronan. View Full-Text
Keywords: hyaluronan; 4-methylumbelliferone; pancreatic ductal adenocarcinoma; extracellular matrices hyaluronan; 4-methylumbelliferone; pancreatic ductal adenocarcinoma; extracellular matrices
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MDPI and ACS Style

Kudo, D.; Suto, A.; Hakamada, K. The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci. 2017, 18, 600. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18030600

AMA Style

Kudo D, Suto A, Hakamada K. The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma. International Journal of Molecular Sciences. 2017; 18(3):600. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18030600

Chicago/Turabian Style

Kudo, Daisuke, Akiko Suto, and Kenichi Hakamada. 2017. "The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma" International Journal of Molecular Sciences 18, no. 3: 600. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18030600

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