Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid

Ingeborg Klaassen, Jacqueline Cloos, Serge J. Smeets, Ruud H. Brakenhoff, Maarten P. Tabor, Gordon B. Snow, Boudewijn J.M. Braakhuis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background and Objective: Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It has been shown that metabolic pathways of retinoids are important in their anticancer effect and that these pathways may change during HNSCC carcinogenesis. We have previously reported that HNSCC cells have a 17-fold greater turnover rate of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only seen in HNSCC cell lines. We aimed to establish whether this altered retinoid metabolism is an intrinsic characteristic of HNSCC patients. Methods: The normal mucosa of cancer and noncancer patients was the source of keratinocyte cultures. The cells were exposed to RA for various time periods, and the levels of various retinoids were measured in the culture medium and cell pellets with reverse-phase liquid chromatography. Results: Cells from cancer patients were morphologically normal and showed no genetic aberrations (i.e. loss of heterozygosity). The RA turnover rate in normal oral keratinocytes of cancer patients was 15 times higher (p = 0.003) than that in normal oral keratinocytes of noncancer controls, with average turnover rates of 218.6 and 14.8 pmol/mg protein/h, respectively. Specific profiles of RA metabolites were similar. Conclusion: The observed higher RA metabolism in noncancer cells of HNSCC patients suggests that individuals with a relatively high RA turnover have an increased risk of developing HNSCC.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalOncology
Volume63
Issue number1
DOIs
Publication statusPublished - 14 Sep 2002

Cite this

Klaassen, Ingeborg ; Cloos, Jacqueline ; Smeets, Serge J. ; Brakenhoff, Ruud H. ; Tabor, Maarten P. ; Snow, Gordon B. ; Braakhuis, Boudewijn J.M. / Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid. In: Oncology. 2002 ; Vol. 63, No. 1. pp. 56-63.
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title = "Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid",
abstract = "Background and Objective: Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It has been shown that metabolic pathways of retinoids are important in their anticancer effect and that these pathways may change during HNSCC carcinogenesis. We have previously reported that HNSCC cells have a 17-fold greater turnover rate of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only seen in HNSCC cell lines. We aimed to establish whether this altered retinoid metabolism is an intrinsic characteristic of HNSCC patients. Methods: The normal mucosa of cancer and noncancer patients was the source of keratinocyte cultures. The cells were exposed to RA for various time periods, and the levels of various retinoids were measured in the culture medium and cell pellets with reverse-phase liquid chromatography. Results: Cells from cancer patients were morphologically normal and showed no genetic aberrations (i.e. loss of heterozygosity). The RA turnover rate in normal oral keratinocytes of cancer patients was 15 times higher (p = 0.003) than that in normal oral keratinocytes of noncancer controls, with average turnover rates of 218.6 and 14.8 pmol/mg protein/h, respectively. Specific profiles of RA metabolites were similar. Conclusion: The observed higher RA metabolism in noncancer cells of HNSCC patients suggests that individuals with a relatively high RA turnover have an increased risk of developing HNSCC.",
keywords = "Cancer risk, Head and neck neoplasms, Head and neck squamous cell carcinoma, Keratinocytes, Metabolism, Premalignancy, Retinoids, Squamous, Tretinoin",
author = "Ingeborg Klaassen and Jacqueline Cloos and Smeets, {Serge J.} and Brakenhoff, {Ruud H.} and Tabor, {Maarten P.} and Snow, {Gordon B.} and Braakhuis, {Boudewijn J.M.}",
year = "2002",
month = "9",
day = "14",
doi = "10.1159/000065721",
language = "English",
volume = "63",
pages = "56--63",
journal = "Oncology",
issn = "0030-2414",
publisher = "S. Karger AG",
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Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid. / Klaassen, Ingeborg; Cloos, Jacqueline; Smeets, Serge J.; Brakenhoff, Ruud H.; Tabor, Maarten P.; Snow, Gordon B.; Braakhuis, Boudewijn J.M.

In: Oncology, Vol. 63, No. 1, 14.09.2002, p. 56-63.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid

AU - Klaassen, Ingeborg

AU - Cloos, Jacqueline

AU - Smeets, Serge J.

AU - Brakenhoff, Ruud H.

AU - Tabor, Maarten P.

AU - Snow, Gordon B.

AU - Braakhuis, Boudewijn J.M.

PY - 2002/9/14

Y1 - 2002/9/14

N2 - Background and Objective: Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It has been shown that metabolic pathways of retinoids are important in their anticancer effect and that these pathways may change during HNSCC carcinogenesis. We have previously reported that HNSCC cells have a 17-fold greater turnover rate of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only seen in HNSCC cell lines. We aimed to establish whether this altered retinoid metabolism is an intrinsic characteristic of HNSCC patients. Methods: The normal mucosa of cancer and noncancer patients was the source of keratinocyte cultures. The cells were exposed to RA for various time periods, and the levels of various retinoids were measured in the culture medium and cell pellets with reverse-phase liquid chromatography. Results: Cells from cancer patients were morphologically normal and showed no genetic aberrations (i.e. loss of heterozygosity). The RA turnover rate in normal oral keratinocytes of cancer patients was 15 times higher (p = 0.003) than that in normal oral keratinocytes of noncancer controls, with average turnover rates of 218.6 and 14.8 pmol/mg protein/h, respectively. Specific profiles of RA metabolites were similar. Conclusion: The observed higher RA metabolism in noncancer cells of HNSCC patients suggests that individuals with a relatively high RA turnover have an increased risk of developing HNSCC.

AB - Background and Objective: Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It has been shown that metabolic pathways of retinoids are important in their anticancer effect and that these pathways may change during HNSCC carcinogenesis. We have previously reported that HNSCC cells have a 17-fold greater turnover rate of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only seen in HNSCC cell lines. We aimed to establish whether this altered retinoid metabolism is an intrinsic characteristic of HNSCC patients. Methods: The normal mucosa of cancer and noncancer patients was the source of keratinocyte cultures. The cells were exposed to RA for various time periods, and the levels of various retinoids were measured in the culture medium and cell pellets with reverse-phase liquid chromatography. Results: Cells from cancer patients were morphologically normal and showed no genetic aberrations (i.e. loss of heterozygosity). The RA turnover rate in normal oral keratinocytes of cancer patients was 15 times higher (p = 0.003) than that in normal oral keratinocytes of noncancer controls, with average turnover rates of 218.6 and 14.8 pmol/mg protein/h, respectively. Specific profiles of RA metabolites were similar. Conclusion: The observed higher RA metabolism in noncancer cells of HNSCC patients suggests that individuals with a relatively high RA turnover have an increased risk of developing HNSCC.

KW - Cancer risk

KW - Head and neck neoplasms

KW - Head and neck squamous cell carcinoma

KW - Keratinocytes

KW - Metabolism

KW - Premalignancy

KW - Retinoids

KW - Squamous

KW - Tretinoin

UR - http://www.scopus.com/inward/record.url?scp=0036368001&partnerID=8YFLogxK

U2 - 10.1159/000065721

DO - 10.1159/000065721

M3 - Article

VL - 63

SP - 56

EP - 63

JO - Oncology

JF - Oncology

SN - 0030-2414

IS - 1

ER -