title: Relation between hyaluronan synthesis and cell morphology in ovarian clear cell carcinomas.
abstract: Ovarian clear cell carcinomas often show a spherule-like mucoid stroma. In ascitic fluid, they form spheroids with a hollow acellular space. In spite of the absence of stromal cells, both the mucoid stroma and hollow spheroids contain abundant extracellular matrix, and one of the major components is hyaluronan. It has been suggested that tumor-derived hyaluronan plays a significant role in the formation of these structures. To clarify this, a hyaluronan inhibition assay was performed on HAC-2, a clear cell carcinoma cell line, in vitro. When hyaluronan synthesis was inhibited by 4-methylumbelliferone, HAC-2 failed to show the spherule-like accumulation of hyaluronan or hollow spheroids. Inhibition of hyaluronan synthesis was associated with the reduction of cell growth. Analysis of 28 archival ascites cytology specimens showed that clear cell carcinomas expressed hyaluronan more frequently than serous carcinomas (11 of 14 vs 3 of 14, respectively, P < 0.05). All of these facts indicate that tumor-derived hyaluronan is essential for the formation of the mucoid stroma or hollow spheroids, and that hyaluronan is also involved in the regulation of cell growth in ovarian clear cell carcinomas. The inhibition of hyaluronan synthesis could be a potential adjunctive therapy for refractory clear cell carcinomas outside the ovary.
authors.affiliation: Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki.
authors.forename: Kasumi
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Pathology, Tsuruoka Municipal Shonai Hospital, Tsuruoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchigasaki
authors.affiliation: Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurose
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000276:Adjuvants, Immunologic / Q000096:biosynthesis*; D001201:Ascites / Q000473:pathology; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D006923:Hymecromone / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000276:Adjuvants, Immunologic; D006923:Hymecromone; D006820:Hyaluronic Acid
keywords: 4-methylumbelliferone; ascites; clear cell carcinoma; hollow spheroid; hyaluronan; ovary