Skip to main content
Erschienen in: European Archives of Oto-Rhino-Laryngology 12/2007

01.12.2007 | Laryngology

Overexpression of transketolase TKTL1 is associated with shorter survival in laryngeal squamous cell carcinomas

verfasst von: Hans-Ullrich Völker, Matthias Scheich, Bernd Schmausser, Ulrike Kämmerer, Matthias Eck

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 12/2007

Einloggen, um Zugang zu erhalten

Abstract

Tumorigenesis involves energy production by aerobic glycolysis (“Warburg effect”) in malignant tumors. One of the key enzymes is transketolase. Transketolase, transketolase-like-1 (TKTL1), and transketolase-like-2 are known. Antibodies against TKTL1 exist for immunohistochemical investigations. This study investigated the influence of TKTL1 on survival and metastasizing in 40 laryngeal squamous cell carcinomas (SCCs, T2–T4, 27 metastasized). Staining was assessed by an immunoreactive score (IRS) with values from 0 to 12 in primaries and their nodal metastases. The highest IRS was 8. Normal epithelium did not show an expression. Three SCCs were negative. Advanced SCCs had a higher IRS than lower stages. An IRS > 4 was associated with a shorter disease specific survival, independent on the tumor stage in the multivariate analysis. Significant differences between metastasized and non-metastasized SCCs were absent, but poorly differentiated SCCs had a higher IRS in their metastases than moderate differentiated SCCs. TKTL1 overexpression is associated with a more aggressive behavior and shorter survival of laryngeal SCCs. These observations could lead to additional therapeutic options targeting a blocking of the enzyme activity.
Literatur
1.
Zurück zum Zitat Boros LG, Bassilian S, Lim S, Lee WN (2001) Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. Pancreas 22:1–7PubMedCrossRef Boros LG, Bassilian S, Lim S, Lee WN (2001) Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. Pancreas 22:1–7PubMedCrossRef
2.
Zurück zum Zitat Comin-Anduix B, Boren J, Martinez S, Moro C, Centelles JJ, Trebukhina R, Petushok N, Lee WN, Boros LG, Cascante M (2001) The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Eur J Biochem 268:4177–4182PubMedCrossRef Comin-Anduix B, Boren J, Martinez S, Moro C, Centelles JJ, Trebukhina R, Petushok N, Lee WN, Boros LG, Cascante M (2001) The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Eur J Biochem 268:4177–4182PubMedCrossRef
3.
Zurück zum Zitat Coy JF, Dressler D, Wilde J, Schubert P (2005) Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Clin Lab 51:257–273PubMed Coy JF, Dressler D, Wilde J, Schubert P (2005) Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Clin Lab 51:257–273PubMed
4.
Zurück zum Zitat Di Chiro G, Hatazawa J, Katz DA, Rizzoli HV, De Michele DJ (1987) Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study. Radiology 164:521–526PubMed Di Chiro G, Hatazawa J, Katz DA, Rizzoli HV, De Michele DJ (1987) Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study. Radiology 164:521–526PubMed
5.
Zurück zum Zitat Dos Santos DT, Pereira Lima EN, Chojniak R, Cavalcanti MG (2005) Topographic metabolic map of head and neck squamous cell carcinoma using 18F-FDG PET and CT image fusion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:619–625PubMedCrossRef Dos Santos DT, Pereira Lima EN, Chojniak R, Cavalcanti MG (2005) Topographic metabolic map of head and neck squamous cell carcinoma using 18F-FDG PET and CT image fusion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:619–625PubMedCrossRef
6.
Zurück zum Zitat Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell derived lactic acid on human T cells. Blood 109(9):3812–3819PubMedCrossRef Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell derived lactic acid on human T cells. Blood 109(9):3812–3819PubMedCrossRef
7.
Zurück zum Zitat Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899PubMedCrossRef Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899PubMedCrossRef
8.
Zurück zum Zitat Haberkorn U, Strauss LG, Reisser C, Haag D, Dimitrakopoulou A, Ziegler S, Oberdorfer F, Rudat V, van Kaick G (1991) Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry. J Nucl Med 32:1548–1555PubMed Haberkorn U, Strauss LG, Reisser C, Haag D, Dimitrakopoulou A, Ziegler S, Oberdorfer F, Rudat V, van Kaick G (1991) Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry. J Nucl Med 32:1548–1555PubMed
9.
Zurück zum Zitat Krockenberger M, Honig A, Rieger L, Coy JF, Sutterlin M, Kapp M, Horn E, Dietl J, Kammerer U (2007) Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases. Int J Gynecol Cancer 17:101–106PubMedCrossRef Krockenberger M, Honig A, Rieger L, Coy JF, Sutterlin M, Kapp M, Horn E, Dietl J, Kammerer U (2007) Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases. Int J Gynecol Cancer 17:101–106PubMedCrossRef
10.
Zurück zum Zitat Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97:1015–1024PubMedCrossRef Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97:1015–1024PubMedCrossRef
11.
Zurück zum Zitat Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, Popa J, Ternullo MP, Steidler A, Weiss C, Grobholz R, Willeke F, Alken P, Stassi G, Schubert P, Coy JF (2006) Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 94:578–585PubMedCrossRef Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, Popa J, Ternullo MP, Steidler A, Weiss C, Grobholz R, Willeke F, Alken P, Stassi G, Schubert P, Coy JF (2006) Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 94:578–585PubMedCrossRef
12.
Zurück zum Zitat Rais B, Comin B, Puigjaner J, Brandes JL, Creppy E, Saboureau D, Ennamany R, Lee WN, Boros LG, Cascante M (1999) Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich’s tumor cells through inhibition of the pentose cycle. FEBS Lett 456:113–118PubMedCrossRef Rais B, Comin B, Puigjaner J, Brandes JL, Creppy E, Saboureau D, Ennamany R, Lee WN, Boros LG, Cascante M (1999) Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich’s tumor cells through inhibition of the pentose cycle. FEBS Lett 456:113–118PubMedCrossRef
13.
Zurück zum Zitat Ramos-Montoya A, Lee WN, Bassilian S, Lim S, Trebukhina RV, Kazhyna MV, Ciudad CJ, Noe V, Centelles JJ, Cascante M (2006) Pentose phosphate cycle oxidative and nonoxidative balance: a new vulnerable target for overcoming drug resistance in cancer. Int J Cancer 119:2733–2741PubMedCrossRef Ramos-Montoya A, Lee WN, Bassilian S, Lim S, Trebukhina RV, Kazhyna MV, Ciudad CJ, Noe V, Centelles JJ, Cascante M (2006) Pentose phosphate cycle oxidative and nonoxidative balance: a new vulnerable target for overcoming drug resistance in cancer. Int J Cancer 119:2733–2741PubMedCrossRef
14.
Zurück zum Zitat Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed
15.
Zurück zum Zitat Schenk G, Duggleby RG, Nixon PF (1998) Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Int J Biochem Cell Biol 30:1297–1318PubMedCrossRef Schenk G, Duggleby RG, Nixon PF (1998) Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Int J Biochem Cell Biol 30:1297–1318PubMedCrossRef
16.
Zurück zum Zitat Shibata K, Kajiyama H, Mizokami Y, Ino K, Nomura S, Mizutani S, Terauchi M, Kikkawa F (2005) Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia. Gynecol Oncol 98:11–18PubMedCrossRef Shibata K, Kajiyama H, Mizokami Y, Ino K, Nomura S, Mizutani S, Terauchi M, Kikkawa F (2005) Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia. Gynecol Oncol 98:11–18PubMedCrossRef
17.
Zurück zum Zitat Smith TA, Titley J (2000) Deoxyglucose uptake by a head and neck squamous carcinoma: influence of changes in proliferative fraction. Int J Radiat Oncol Biol Phys 47:219–223PubMedCrossRef Smith TA, Titley J (2000) Deoxyglucose uptake by a head and neck squamous carcinoma: influence of changes in proliferative fraction. Int J Radiat Oncol Biol Phys 47:219–223PubMedCrossRef
18.
Zurück zum Zitat Staiger WI, Coy JF, Grobholz R, Hofheinz RD, Lukan N, Post S, Schwarzbach MH, Willeke F (2006) Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer. Oncol Rep 16:657–661PubMed Staiger WI, Coy JF, Grobholz R, Hofheinz RD, Lukan N, Post S, Schwarzbach MH, Willeke F (2006) Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer. Oncol Rep 16:657–661PubMed
19.
Zurück zum Zitat Stern R, Shuster S, Neudecker BA, Formby B (2002) Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited. Exp Cell Res 276:24–31PubMedCrossRef Stern R, Shuster S, Neudecker BA, Formby B (2002) Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited. Exp Cell Res 276:24–31PubMedCrossRef
20.
Zurück zum Zitat Tosi L, Rinaldi E, Carinci F, Farina A, Pastore A, Pelucchi S, Cassano L, Evangelisti R, Carinci P, Volinia S (2005) Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma. Head Neck 27:130–137PubMedCrossRef Tosi L, Rinaldi E, Carinci F, Farina A, Pastore A, Pelucchi S, Cassano L, Evangelisti R, Carinci P, Volinia S (2005) Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma. Head Neck 27:130–137PubMedCrossRef
21.
Zurück zum Zitat Walenta S, Schroeder T, Mueller-Klieser W (2004) Lactate in solid malignant tumors: potential basis of a metabolic classification in clinical oncology. Curr Med Chem 11:2195–2204PubMed Walenta S, Schroeder T, Mueller-Klieser W (2004) Lactate in solid malignant tumors: potential basis of a metabolic classification in clinical oncology. Curr Med Chem 11:2195–2204PubMed
22.
Zurück zum Zitat Warburg O, Posener K, Negelein E (1924) Über den Stoffwechsel der Carcinomzelle. Biochem Z 152:309–344 Warburg O, Posener K, Negelein E (1924) Über den Stoffwechsel der Carcinomzelle. Biochem Z 152:309–344
23.
Zurück zum Zitat Weiner MF, Miranda RN, Bardales RH, Mukunyadzi P, Baker SJ, Korourian S, De Las Casas LE (2004) Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy material. Diagn Cytopathol 31:294–299PubMedCrossRef Weiner MF, Miranda RN, Bardales RH, Mukunyadzi P, Baker SJ, Korourian S, De Las Casas LE (2004) Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy material. Diagn Cytopathol 31:294–299PubMedCrossRef
24.
Zurück zum Zitat Williams AC, Collard TJ, Paraskeva C (1999) An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene 18:3199–3204PubMedCrossRef Williams AC, Collard TJ, Paraskeva C (1999) An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene 18:3199–3204PubMedCrossRef
25.
Zurück zum Zitat Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621PubMedCrossRef Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621PubMedCrossRef
Metadaten
Titel
Overexpression of transketolase TKTL1 is associated with shorter survival in laryngeal squamous cell carcinomas
verfasst von
Hans-Ullrich Völker
Matthias Scheich
Bernd Schmausser
Ulrike Kämmerer
Matthias Eck
Publikationsdatum
01.12.2007
Verlag
Springer-Verlag
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 12/2007
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-007-0394-x

Weitere Artikel der Ausgabe 12/2007

European Archives of Oto-Rhino-Laryngology 12/2007 Zur Ausgabe

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Betalaktam-Allergie: praxisnahes Vorgehen beim Delabeling

16.05.2024 Pädiatrische Allergologie Nachrichten

Die große Mehrheit der vermeintlichen Penicillinallergien sind keine. Da das „Etikett“ Betalaktam-Allergie oft schon in der Kindheit erworben wird, kann ein frühzeitiges Delabeling lebenslange Vorteile bringen. Ein Team von Pädiaterinnen und Pädiatern aus Kanada stellt vor, wie sie dabei vorgehen.

Klinikreform soll zehntausende Menschenleben retten

15.05.2024 Klinik aktuell Nachrichten

Gesundheitsminister Lauterbach hat die vom Bundeskabinett beschlossene Klinikreform verteidigt. Kritik an den Plänen kommt vom Marburger Bund. Und in den Ländern wird über den Gang zum Vermittlungsausschuss spekuliert.

Eingreifen von Umstehenden rettet vor Erstickungstod

15.05.2024 Fremdkörperaspiration Nachrichten

Wer sich an einem Essensrest verschluckt und um Luft ringt, benötigt vor allem rasche Hilfe. Dass Umstehende nur in jedem zweiten Erstickungsnotfall bereit waren, diese zu leisten, ist das ernüchternde Ergebnis einer Beobachtungsstudie aus Japan. Doch es gibt auch eine gute Nachricht.

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.