Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors

Franzmann, Elizabeth; Schroeder, G.; Goodwin, W. Jarrard; Weed, Donald T.; Fisher, Penelope; Lokeshwar, Vinata B.

doi:10.1002/ijc.11252

Cited by 139 publications

(120 citation statements)

References 54 publications

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“…HA (i.e., HA fragments) species are present in the saliva of high-stage head-and-neck squamous cell carcinoma patients but not in the saliva of normal individuals. 8 Taken together, our findings and those of Dr. Kumar's group show that, in addition to the increased amounts of HA in cancer patients' body fluids (i.e., urine, serum and saliva) and tumor tissues, the size profile of HA species may be important in cancer diagnosis and for evaluating the biologic behavior of various tumors.…”

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confidence: 75%

Clinical and biologic relevance of hyaluronic acid and its fragments

Lokeshwar¹

2004

Intl Journal of Cancer

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Dear Sir, I thank Dr. Slevin and coauthors for writing an excellent account of the clinical and biologic relevance of hyaluronic acid (HA) and its fragments. In 1985, the seminal work from Dr. Kumar's group offered a glimpse of the role of HA fragments in angiogenesis. 1 In later years, the same group helped to elucidate some of the signal transduction mechanisms by which HA fragments stimulate bovine endothelial cell proliferation, migration and adhesion. 2 Consistent with the findings of Dr. Kumar's group, we previously demonstrated that HA fragments of 10 -15 disaccharide units induce proliferation and adhesion of human primary endothelial cells. 3 Furthermore, primary cultures of human pulmonary artery (HPAEC), lung microvessel (HMVEC-L) and umbilical vein-derived (HUVEC) endothelial cells show differential responsiveness to angiogenic HA fragments. While angiogenic fragments stimulate DNA synthesis in HMVEC-L and HPAEC, HUVEC do not respond to angiogenic HA fragments. 3 However, in contrast to the suggestion by Dr. Kumar's group that the biologic effects of angiogenic HA fragments and HA, observed in bovine endothelial cells, are mediated through cell surface CD44 receptors, 4 we found that RHAMM is the functional cell surface HA receptor expressed in HPAEC and HMVEC-L. RHAMMangiogenic HA fragment interaction induces tyrosine phosphorylation of p125FAK, paxillin and p42/44 ERK. 3 It is likely that the angiogenic HA fragments stimulate proliferation of primary human endothelial cells through the MAP kinase pathway. 3 Thus, it is possible that, in different cell types, angiogenic HA fragments mediate their biologic effects through different HA receptors.Regarding the findings of Dr. Kumar's group that, although HA levels are elevated in the sera of both Wilms' tumor patients and children with bone-metastasizing renal tumor of childhood (BMRTC), HA fragments are found only in the sera of BMRTC patients, 5 our findings in cancers of the bladder, prostate and head/neck are in agreement. 6 -8 We found that HA levels are elevated in the urine of bladder cancer patients regardless of tumor grade [i.e., low (G1), intermediate (G2) and high (G3)]. However, angiogenic HA fragments are found only in the urine of patients with G2 or G3 bladder tumors. 6 This finding could be explained by our observation that hyaluronidase levels are elevated only in G2 and G3 patients, which in turn could degrade tumor-associated HA into angiogenic fragments. We have also shown that in bladder tumor tissues HA is produced by both tumor stroma and tumor cells, whereas hyaluronidase (i.e., HYAL1 gene product) is produced only by tumor cells. 9,10 Also, we found that angiogenic HA fragments are present in high-grade prostate cancer tissues, which contain high levels of both HA and hyaluronidase. 7 In our previous article, we demonstrated that both high and low m.w. HA (i.e., HA fragments) species are present in the saliva of high-stage head-and-neck squamous cell carcinoma patients but not in the saliva of normal individuals. 8 Taken toge...

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confidence: 75%

Clinical and biologic relevance of hyaluronic acid and its fragments

Lokeshwar¹

2004

Intl Journal of Cancer

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“…Altered expression profiles of the Hyal and HAS proteins have been associated with many types of cancers (3)(4)(5)(6)(7). Detection of elevated expression of Hyal1 and concurrent accumulation of HA in biopsies are an indicator of poor prognosis for prostate cancer (8).…”

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Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking

McAtee

Berkebile

Elowsky

et al. 2015

Journal of Biological Chemistry

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Background: Hyal1 is a turnover enzyme for hyaluronan that accelerates metastatic cancer by increasing cell motility. Results: Hyal1-overexpressing cells have a higher rate of endocytosis that impacts cargo internalization and recycling. Conclusion: The higher rate of vesicle trafficking increases motility receptor function and nutrient uptake. Significance: This novel mechanism implicates Hyal1 trafficking in multiple signaling events during tumor progression.

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“…[54] Also, previous few studies reported high levels of in HNSCC. [55,56] In contrast, the HA expression is low in melanoma, and its absence is significantly correlated with the metastatic potential. [57,58] Accumulation of HA can decrease tumorigenic potential and confer resistance to cancer.…”

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confidence: 99%

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

Hendawy

Ibrahiem

et al. 2017

JST

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Background: Epithelial-mesenchymal transition (EMT) is regarded as an essential step for tumor invasion and metastasis. In squamous cell carcinoma of head and neck (HNSCC), N-Cadherin expression and its involvement in tumor progression remains a controversial topic. Aim of the study: The present study aimed to assess the expression of N-cadherin and HA in HNSCC and further study their relation to patients survival and outcomes. Material and methods: Fifty-eight retrospective selected cases of head and neck squamous carcinomas (HNSCCs) with available paraffin blocks. Complete clinico-pathological and follow-up data were recorded. Immune staining for N-cadherin and hyaluronan were done, also, we study the correlation of the results with patients survival data. Results: Squamous cell carcinoma islands demonstrated high N-cadherin expression in 55.2% and low expression in 44.8%. N-cadherin high expression was significantly (p < .05) associated with large tumor sizes, advanced TNM clinical stage, increased incidence of recurrence and patient's death. A significant correlation was recorded between the presence of neural invasion and N-cadherin expression (p = .004). Strong intensity of stromal HA was significantly (p < .05) associated with an oral site, nodal metastasis, and higher TNM stage. Patients with high N-cadherin expression, diffuse hyaluronan, and strong stromal hyaluronan reaction had significantly lower DFS rates (p < .05). High N-cadherin expression, diffuse hyaluronan immunoreactivity, and strong stromal hyaluronan reaction intensity had significantly lower OS rates (p < .05). Conclusion: N-cadherin and hyaluronan could be important and promising biomarkers during surveillance of patients with HNSCC.

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Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors

Cited by 139 publications

References 54 publications

Clinical and biologic relevance of hyaluronic acid and its fragments

Clinical and biologic relevance of hyaluronic acid and its fragments

Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

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