Topical Chemoprophylaxis of Superficial Bladder Cancer with Mitomycin C and Adjuvant Hyaluronidase

Höbarth, K.; Maier, Ulrich; Marberger, M.

doi:10.1159/000474839

Cited by 58 publications

(22 citation statements)

References 12 publications

(15 reference statements)

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“…Moreover, endogenous HA produced by breast cancer cells induces a complex between CD44 and RHAMM, which then recruits extracellular signal-regulated kinase 1/2 in the complex and stimulates its kinase activity (22). HA may also aid tumor cells in overcoming the contact inhibition of growth and avoiding immune surveillance (23,24).…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

Golshani¹,

et al. 2008

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“…In tumor tissues, hyaluronic acid swells on hydration and opens up spaces for tumor cell migration, and tumor cells migrate on hyaluronic acid-rich matrix by interacting with hyaluronic acid receptors (10,11). A hyaluronic acid coat around tumor cells causes a partial loss of contact-mediated growth and migration and offers protection against immune surveillance (20)(21)(22)(23). Small fragments of hyaluronic acid (i.e., 3-25 disaccharide units) are angiogenic (24,25).…”

Section: Introductionmentioning

confidence: 99%

HYAL1 Hyaluronidase: A Molecular Determinant of Bladder Tumor Growth and Invasion

Cerwinka²,

2005

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Hyaluronic acid and HYAL1-type hyaluronidase show high accuracy in detecting bladder cancer and evaluating its grade, respectively. Hyaluronic acid promotes tumor progression; however, the functions of hyaluronidase in cancer are largely unknown. In this study, we stably transfected HT1376 bladder cancer cells with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector cDNA constructs. Whereas HYAL1-S transfectants produced 3-fold more HYAL1 than vector transfectants, HYAL1-AS transfectants showed f f 90% reduction in HYAL1 production. HYAL1-AS transfectants grew four times slower than vector and HYAL1-S transfectants and were blocked in the G 2 -M phase of the cell cycle. The expression of cdc25c and cyclin B1 and cdc2/p34-associated H1 histone kinase activity also decreased in HYAL1-AS transfectants. HYAL1-S transfectants were 30% to 44% more invasive, and HYAL1-AS transfectants were f f 50% less invasive than the vector transfectants in vitro. In xenografts, there was a 4-to 5-fold delay in the generation of palpable HYAL1-AS tumors, and the weight of HYAL1-AS tumors was 9-to 17-fold less than vector and HYAL1-S tumors, respectively (P < 0.001). Whereas HYAL1-S and vector tumors infiltrated skeletal muscle and blood vessels, HYAL1-AS tumors resembled benign neoplasia. HYAL1-S and vector tumors expressed significantly higher amounts of HYAL1 (in tumor cells) and hyaluronic acid (in tumor-associated stroma) than HYAL1-AS tumors. Microvessel density in HYAL1-S tumors was 3.8-and 9.5-fold higher than that in vector and HYAL1-AS tumors, respectively. These results show that HYAL1 expression in bladder cancer cells regulates tumor growth and progression and therefore serves as a marker for high-grade bladder cancer. (Cancer Res 2005; 65(6): 2243-50)

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“…In prostate cancer tissues, hyaluronic acid is mainly produced by tumor-associated stroma; however, f40% of tumor cells express hyaluronic acid (11,12). Tumor-associated hyaluronic acid promotes tumor cell migration, aids in the loss of contact inhibition, and offers protection against immune surveillance (13)(14)(15). Small hyaluronic acid fragments (3-25 disaccharide units), generated by hyaluronidase, are angiogenic (16,17).…”

Section: Introductionmentioning

confidence: 99%

HYAL1 Hyaluronidase in Prostate Cancer: A Tumor Promoter and Suppressor

Lokeshwar

Cerwinka²,

Isoyama³

et al. 2005

Cancer Research

153

162

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Hyaluronidases degrade hyaluronic acid, which promotes metastasis. HYAL1 type hyaluronidase is an independent prognostic indicator of prostate cancer progression and a biomarker for bladder cancer. However, it is controversial whether hyaluronidase (e.g., HYAL1) functions as a tumor promoter or as a suppressor. We stably transfected prostate cancer cells, DU145 and PC-3 ML, with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector DNA. HYAL1-AS transfectants were not generated for PC-3 ML because it expresses little HYAL1. HYAL1-S transfectants produced V42 milliunits (moderate overproducers) or z80 milliunits hyaluronidase activity (high producers). HYAL1-AS transfectants produced <10% hyaluronidase activity when compared with vector transfectants (18-24 milliunits). Both blocking HYAL1 expression and high HYAL1 production resulted in a 4-to 5-fold decrease in prostate cancer cell proliferation. HYAL1-AS transfectants had a G 2 -M block due to decreased cyclin B1, cdc25c, and cdc2/p34 expression and cdc2/p34 kinase activity. High HYAL1 producers had a 3-fold increase in apoptotic activity and mitochondrial depolarization when compared with vector transfectants and expressed activated proapoptotic protein WOX1. Blocking HYAL1 expression inhibited tumor growth by 4-to 7-fold, whereas high HYAL1 producing transfectants either did not form tumors (DU145) or grew 3.5-fold slower (PC-3 ML). Whereas vector and moderate HYAL1 producers generated muscle and blood vessel infiltrating tumors, HYAL1-AS tumors were benign and contained smaller capillaries. Specimens of high HYAL1 producers were 99% free of tumor cells. This study shows that, depending on the concentration, HYAL1 functions as a tumor promoter and as a suppressor and provides a basis for anti-hyaluronidase and high-hyaluronidase treatments for cancer. (Cancer Res 2005; 65(17): 7782-9)

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Topical Chemoprophylaxis of Superficial Bladder Cancer with Mitomycin C and Adjuvant Hyaluronidase

Cited by 58 publications

References 12 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

HYAL1 Hyaluronidase: A Molecular Determinant of Bladder Tumor Growth and Invasion

HYAL1 Hyaluronidase in Prostate Cancer: A Tumor Promoter and Suppressor

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