Hyaluronan synthase expression in ovarian cancer

Yabushita, Hiromitsu; Noguchi, M.; Kishida, Tameko; Fusano, Kanako; Noguchi, Yasuyuki; Itano, Naoki; Kimata, Koji; Noguchi, Masayoshi

doi:10.3892/or.12.4.739

Cited by 39 publications

(49 citation statements)

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“…Taken together, these findings show that the tumor-associated HA-HYAL1 system is important in tumor growth and progression. HAS1 expression correlates with invasion, disease progression, tumor recurrence, and poor survival in a variety of carcinomas, including bladder (6,(35)(36)(37)(38). The results presented in this study show that HAS1 is a positive regulator of tumor growth progression, and therefore, it may be an accurate diagnostic and prognostic tumor marker and a possible therapeutic target.…”

Section: Discussionmentioning

confidence: 78%

“…The expression of a HAS1 splice variant (HAS1-vb) has been shown to correlate with survival in multiple myeloma patients (35). HAS1 expression in tumor tissues also serves as a prognostic indicator in many carcinomas (6,(34)(35)(36)(37). We have shown that, in bladder cancer, HAS1 mRNA and protein expression is elevated in bladder tumor cells and tissues and correlates with a positive inference on the HA urine test.…”

Section: Introductionmentioning

confidence: 71%

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Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44

Golshani¹,

et al. 2008

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Hyaluronic acid (HA) promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. HA is synthesized by HA synthases HAS1, HAS2, or HAS3. We have previously shown that HAS1 expression in tumor tissues is a predictor of bladder cancer recurrence and treatment failure. In this study, we stably transfected HT1376 bladder cancer cells with HAS1-sense (HAS1-S), HAS1-antisense (HAS1-AS), or vector cDNA constructs. Whereas HAS1-S transfectants produced f1.7-fold more HA than vector transfectants, HA production was reduced by f70% in HAS1-AS transfectants. HAS1-AS transfectants grew 5-fold slower and were f60% less invasive than vector and HAS1-S transfectants. HAS1-AS transfectants were blocked in G 2 -M phase of the cell cycle due to down-regulation of cyclin B1, cdc25c, and cyclin-dependent kinase 1 levels. These transfectants were also 5-to 10-fold more apoptotic due to the activation of the Fas-Fas ligandmediated extrinsic pathway. HAS1-AS transfectants showed a f4-fold decrease in ErbB2 phosphorylation and downregulation of CD44 variant isoforms (CD44-v3, CD44-v6, and CD44-E) both at the protein and mRNA levels. However, no decrease in RHAMM levels was observed. The decrease in CD44-v mRNA levels was not due to increased mRNA degradation. Whereas CD44 small interfering RNA (siRNA) transfection decreased cell growth and induced apoptosis in HT1376 cells, HA addition modestly increased CD44 expression and cell growth in HAS1-AS transfectants, which could be blocked by CD44 siRNA. In xenograft studies, HAS1-AS tumors grew 3-to 5-fold slower and had f4-fold lower microvessel density. These results show that HAS1 regulates bladder cancer growth and progression by modulating HA synthesis and HA receptor levels. [Cancer Res 2008;68(2):483-91]

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 71%

Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44

Golshani¹,

et al. 2008

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“…Several investigators reported that both the glycosaminoglycan HA and the decoy receptor DcR3 could be key players in tumor development (33)(34)(35)(36)(37). It was demonstrated that HA is released by tumor cells and blocks the inflammatory signaling in human monocytes (34, 37); DcR3 can be defined as an immunomodulator on the basis of its neu- tralizing effects on FasL, LIGHT, and TL1A.…”

Section: Soluble Factors With Putative Involvement In the Observed Etmentioning

confidence: 99%

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Jurado-Camino

Esteban-Burgos

Hernández-Jiménez

et al. 2015

The Journal of Immunology

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Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors.

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“…The glycosaminoglycan is attached to the membranes of several cancer cells, but is also released by these cells as a soluble factor in culture (37)(38)(39). To study the possible role of HA in the up-regulation of IRAK-M by tumor cells, human monocytes were stimulated with two different concentrations of soluble HA.…”

Section: Ha Induces Irak-m Mrna Expressionmentioning

confidence: 99%

Tumor Cells Deactivate Human Monocytes by Up-Regulating IL-1 Receptor Associated Kinase-M Expression via CD44 and TLR4

Fresno

Otero

Gómez-García

et al. 2005

The Journal of Immunology

129

115

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Although blood monocytes possess significant cytotoxic activity against tumor cells, tumor-infiltrating monocytes are commonly deactivated in cancer patients. Monocytes pre-exposed to tumor cells show significantly decreased expression levels of TNF-α, IL-12p40, and IL-1R-associated kinase (IRAK)-1. Activation of the Ser/Thr kinase IRAK-1 is an important event in several inflammatory processes. By contrast, another IRAK family member, IRAK-M, negatively regulates this pathway, and is up-regulated in cultures of endotoxin-tolerant monocytes and in monocytes from septic patients within the timeframe of tolerance. In this study, we show that IRAK-M expression is enhanced at the mRNA and protein level in human monocytes cultured in the presence of tumor cells. IRAK-M was induced in monocytes upon coculturing with different tumor cells, as well as by fixed tumor cells and medium supplemented with the supernatant from tumor cell cultures. Moreover, blood monocytes from patients with chronic myeloid leukemia and patients with metastasis also overexpressed IRAK-M. Low concentrations of hyaluronan, a cell surface glycosaminoglycan released by tumor cells, also up-regulated IRAK-M. The induction of IRAK-M by hyaluronan and tumor cells was abolished by incubation with anti-CD44 or anti-TLR4 blocking Abs. Furthermore, down-regulation of IRAK-M expression by small interfering RNAs specific for IRAK-M reinstates both TNF-α mRNA expression and protein production in human monocytes re-exposed to a tumor cell line. Altogether, our findings indicate that deactivation of human monocytes in the presence of tumor cells involves IRAK-M up-regulation, and this effect appears to be mediated by hyaluronan through the engagement of CD44 and TLR4.

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Hyaluronan synthase expression in ovarian cancer

Cited by 39 publications

References 0 publications

Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44

Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Tumor Cells Deactivate Human Monocytes by Up-Regulating IL-1 Receptor Associated Kinase-M Expression via CD44 and TLR4

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