Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate

Lp, Setälä; Mi, Tammi; Rh, Tammi; Mj, Eskelinen; Pk, Lipponen; Um, Agren; Parkkinen, Jyrki; Em, Alhava; Kosma, Veli‐Matti

doi:10.1038/sj.bjc.6690180

Cited by 147 publications

(73 citation statements)

References 29 publications

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“…[13][14][15][16][17][18][19] We found that the HA staining had 92.3% sensitivity and 80.6% specificity to predict biochemical recurrence within 112 months. Interestingly, the specificity of HA staining to predict biochemical recurrence increased from 61% at 72-month follow-up to 80.6% at 112-month follow-up.…”

Section: Evaluation Of the Prognostic Capability Of Pre-and Postoperamentioning

confidence: 99%

“…14 The concentration of HA is elevated in several tumor types, and in some tumors (e.g., breast, colon), high-level HA expression in tumor-associated stroma and/or tumor cells predicts poor survival. [15][16][17][18][19] Increased urinary HA levels serve as an accurate diagnostic marker for bladder cancer, regardless of tumor grade and stage. 20 However, in PCa, HA is not an independent predictor for prognosis.…”

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confidence: 99%

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Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Ekici

Cerwinka

Duncan

et al. 2004

Intl Journal of Cancer

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Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis.

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Section: Evaluation Of the Prognostic Capability Of Pre-and Postoperamentioning

confidence: 99%

mentioning

confidence: 99%

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Ekici

Cerwinka

Duncan

et al. 2004

Intl Journal of Cancer

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“…Accumulation of HA has been reported in a wide variety of human tumors, including those of the prostate, colon, breast, stomach, ovary, and pancreas (6)(7)(8)(9)(10)(11)(12). Elevated HA (stromal and/or pericellular staining) in tumor biopsies has been correlated with local invasion, the presence of distal metastasis, higher tumor grade, and poorer overall survival (13).…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Thompson

Shepard²,

O’Connor³

et al. 2010

Molecular Cancer Therapeutics

255

278

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Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells. The therapeutic potential of enzymatic remodeling of the tumor microenvironment through HA depletion was initially investigated using a recombinant human HA-degrading enzyme, rHuPH20, which removed HA-dependent tumor cell extracellular matrices in vitro. However, rHuPH20 showed a short serum half-life (t 1/2 < 3 minutes), making depletion of tumor HA in vivo impractical. A pegylated variant of rHuPH20, PEGPH20, was therefore evaluated. Pegylation improved serum half-life (t 1/2 = 10.3 hours), making it feasible to probe the effects of sustained HA depletion on tumor physiology. In high-HA prostate PC3 tumors, i.v. administration of PEGPH20 depleted tumor HA, decreased tumor interstitial fluid pressure by 84%, decreased water content by 7%, decompressed tumor vessels, and increased tumor vascular area >3-fold. Following repeat PEGPH20 administration, tumor growth was significantly inhibited (tumor growth inhibition, 70%). Furthermore, PEGPH20 enhanced both docetaxel and liposomal doxorubicin activity in PC3 tumors (P < 0.05) but did not significantly improve the activity of docetaxel in low-HA prostate DU145 tumors. The ability of PEGPH20 to enhance chemotherapy efficacy is likely due to increased drug perfusion combined with other tumor structural changes. These results support enzymatic remodeling of the tumor stroma with PEGPH20 to treat tumors characterized by the accumulation of HA. Mol Cancer Ther; 9(11); 3052-64. ©2010 AACR.

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“…Concentrations of hyaluronic acid are elevated in cancers of the breast, colon, prostate, bladder, etc. (8,(12)(13)(14)(15)(16)(17)(18). In tumor tissues, elevated hyaluronic acid is mostly localized to tumor stroma; however, in some tumors, including bladder cancer, it is also expressed in tumor cells (12)(13)(14)(15)(16)(17)(18).…”

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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Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate

Cited by 147 publications

References 29 publications

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

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

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