title: Hyaluromycin, a Novel Hyaluronidase Inhibitor, Attenuates Pancreatic Cancer Cell Migration and Proliferation.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derivedStreptomyces hyaluromycinias a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm.
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kohi
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Norihiro
authors.identifier: 0000-0002-2739-9790
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Koga
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, Toyama, Japan.
authors.forename: Enjuro
authors.initials: E
authors.lastname: Harunari
authors.affiliation: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, Toyama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi