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

Elizabeth J. Franzmann, Grethchen L. Schroeder, William Jarrard Goodwin, Donald T. Weed, Penelope Fisher, Vinata B Lokeshwar

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in II HNSCC patients (2841 ± 887 ng/mg protein) when compared to 6 normal controls (579.3 ± 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 t 1.4 mU/mg protein) when compared to normal controls (2.8 ± 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a ∼55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalInternational Journal of Cancer
Volume106
Issue number3
DOIs
StatePublished - Sep 1 2003

Fingerprint

Hyaluronoglucosaminidase
Hyaluronic Acid
Tumor Biomarkers
Neck
Head
Saliva
Neoplasms
Conditioned Culture Medium
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Recurrence
Enzyme-Linked Immunosorbent Assay
Carcinoma, squamous cell of head and neck
Neoplasm Metastasis
Glycoside Hydrolases
Mouth Neoplasms
Larynx
Pharynx
Keratinocytes
Extracellular Matrix

Keywords

  • HA-HAase test
  • HYAL1
  • Head and neck tumors
  • Hyaluronic acid
  • Hyaluronidase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. / Franzmann, Elizabeth J.; Schroeder, Grethchen L.; Goodwin, William Jarrard; Weed, Donald T.; Fisher, Penelope; Lokeshwar, Vinata B.

In: International Journal of Cancer, Vol. 106, No. 3, 01.09.2003, p. 438-445.

Research output: Contribution to journalArticle

Franzmann, Elizabeth J. ; Schroeder, Grethchen L. ; Goodwin, William Jarrard ; Weed, Donald T. ; Fisher, Penelope ; Lokeshwar, Vinata B. / Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. In: International Journal of Cancer. 2003 ; Vol. 106, No. 3. pp. 438-445.
@article{9e7efe809f504c61a9ada53a1898eed2,
title = "Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors",
abstract = "Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in II HNSCC patients (2841 ± 887 ng/mg protein) when compared to 6 normal controls (579.3 ± 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 t 1.4 mU/mg protein) when compared to normal controls (2.8 ± 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a ∼55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.",
keywords = "HA-HAase test, HYAL1, Head and neck tumors, Hyaluronic acid, Hyaluronidase",
author = "Franzmann, {Elizabeth J.} and Schroeder, {Grethchen L.} and Goodwin, {William Jarrard} and Weed, {Donald T.} and Penelope Fisher and Lokeshwar, {Vinata B}",
year = "2003",
month = "9",
day = "1",
doi = "10.1002/ijc.11252",
language = "English (US)",
volume = "106",
pages = "438--445",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors

AU - Franzmann, Elizabeth J.

AU - Schroeder, Grethchen L.

AU - Goodwin, William Jarrard

AU - Weed, Donald T.

AU - Fisher, Penelope

AU - Lokeshwar, Vinata B

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in II HNSCC patients (2841 ± 887 ng/mg protein) when compared to 6 normal controls (579.3 ± 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 t 1.4 mU/mg protein) when compared to normal controls (2.8 ± 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a ∼55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.

AB - Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in II HNSCC patients (2841 ± 887 ng/mg protein) when compared to 6 normal controls (579.3 ± 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 t 1.4 mU/mg protein) when compared to normal controls (2.8 ± 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a ∼55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.

KW - HA-HAase test

KW - HYAL1

KW - Head and neck tumors

KW - Hyaluronic acid

KW - Hyaluronidase

UR - http://www.scopus.com/inward/record.url?scp=0037491618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037491618&partnerID=8YFLogxK

U2 - 10.1002/ijc.11252

DO - 10.1002/ijc.11252

M3 - Article

VL - 106

SP - 438

EP - 445

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -