nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.06.2013 | Original Paper

Increase of N ¹ ,N ¹²-diacetylspermine in tissues from colorectal cancer and its liver metastasis

verfasst von: Go Kuwata, Kyoko Hiramatsu, Keijiro Samejima, Kaori Iwasaki, Kei-ichi Takahashi, Koichi Koizumi, Shin-ichiro Horiguchi, Shun-suke Moriya, Masaki Kobayashi, Masao Kawakita

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

N ¹ ,N ¹²-Diacetylspermine (DiAcSpm) is a tumor marker featured by increase in the urine of patients with cancers, including early colorectal cancer, but where and how DiAcSpm is made remains unclear. We aimed to clarify whether colorectal cancer tissues produce increased amounts of DiAcSpm, and if they do, to examine whether tissue DiAcSpm level may serve as a criterion of tissue malignancy.

Methods

Tissue samples were obtained from 140 patients (13 low-grade intraepithelial neoplasia, 98 high-grade intraepithelial neoplasia and 29 colorectal cancer) treated for colorectal cancer and intraepithelial neoplasia at Tokyo Metropolitan Komagome Hospital between November 2007 and April 2011. The DiAcSpm level in cancer and adjacent normal tissue extracts was compared, and its relationship with clinical stages of the diseases was analyzed.

Results

DiAcSpm levels were higher in colorectal cancer tissue (p < 0.01, n = 12) and its liver metastasis (p < 0.05, n = 5) than in adjacent normal tissues. The tumor/normal ratio of tissue DiAcSpm content was examined for endoscopically obtained tumor and adjacent normal tissues from patients with intraepithelial neoplasia. The ratio was greater than 1.5 in 38 % (5/13) and 78 % (84/108) of low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia, respectively.

Conclusions

Tissue DiAcSpm levels increase in the tissue of colorectal cancer and also in precancerous lesion, such as high-grade intraepithelial neoplasia. The increase is considered a sign that a tissue is acquiring malignant characteristics. It is likely that the DiAcSpm produced by cancer cells is responsible for the frequent increase in urinary DiAcSpm in early cancer patients.

Hamaoki M, Nagata A (2006) Host macrophages produce diacetylspermine related with tumorigenesis. Cancer Lett 243:128–134PubMedCrossRef

Hiramatsu K, Kamei S, Sugimoto M, Kinoshita K, Iwasaki K, Kawakita M (1994) An improved method of determining free and acetylated polyamines by HPLC involving an enzyme reactor and an electrochemical detector. J Biochem 115:584–589PubMed

Hiramatsu K, Sugimoto M, Kamei S, Hoshino M, Kinoshita K, Iwasaki K, Kawakita M (1995) Determination of amounts of polyamines excreted in urine: demonstration of N ¹, N ⁸-diacetylspermidine and N ¹,N ¹²-diacetylspermine as components commonly occurring in normal human urine. J Biochem 117:107–112PubMed

Hiramatsu K, Sugimoto M, Kamei S, Hoshino M, Kinoshita K, Iwasaki K, Kawakita M (1997) Diagnostic and prognostic usefulness of N ¹, N ⁸-diacetylspermidine and N ¹,N ¹²-diacetylspermine in urine as novel markers of malignancy. J Cancer Res Clin Oncol 123:539–545PubMedCrossRef

Hiramatsu K, Takahashi K, Yamaguchi T, Matsumoto H, Miyamoto H, Tanaka S, Tanaka C, Tamamori Y, Imajo M, Kawaguchi M, Toi M, Mori T, Kawakita M (2005) N ¹,N ¹²-diacetylspermine as a sensitive and specific novel marker for early- and late-stage colorectal and breast cancers. Clin Cancer Res 11:2986–2990PubMedCrossRef

Kawakita M, Hiramatsu K (2006) Diacetylated derivatives of spermine and spermidine as novel promising tumor markers. J Biochem 139:315–322PubMedCrossRef

Kawakita M, Hiramatsu K, Yanagiya M, Doi Y, Kosaka M (2011) Determination of N ¹,N ¹²-diacetylspermine in urine: a novel tumor marker. In: Pegg AE, Casero RA (eds) Methods in molecular biology vol. 720. Humana Press, New York, pp 367–378

Kingsnorth AN, Wallace HM (1985) Elevation of monoacetylated polyamines in human breast cancers. Eur J Cancer Clin Oncol 21:1057–1062PubMedCrossRef

Kobayashi M, Samejima K, Hiramatsu K, Kawakita M (2002) Mass spectrometric separation and determination of N ¹,N ¹²-diacetylspermine in the urine of cancer patients. Biol Pharm Bull 25:372–374PubMedCrossRef

Miki T, Hiramatsu K, Kawakita M (2005) Interaction of N ¹,N ¹²-diacetylspermine with polyamine transport systems of polarized porcine renal cell line LLC-PK1. J Biochem 138:479–484PubMedCrossRef

Samejima K, Otani M, Murakami Y, Oka T, Kasai M, Tsumoto H, Kohda K (2007) Electrospray ionization and time-of-flight mass spectrometric method for simultaneous determination of spermidine and spermine. Biol Pharm Bull 30:1943–1946PubMedCrossRef

Samejima K, Hiramatsu K, Takahashi K, Kawakita M, Kobayashi M, Tsumoto H, Kohda K (2010) Identification and determination of urinary acetylpolyamines in cancer patients by electrospray ionization and time-of-flight mass spectrometry. Anal Biochem 401:22–29PubMedCrossRef

Sugimoto M, Hiramatsu K, Kamei S, Kinoshita K, Hoshino M, Iwasaki K, Kawakita M (1995) Significance of urinary N1, N8-diacetylspermidine and N ¹,N ¹²-diacetylspermine as indicators of neoplastic diseases. J Cancer Res Clin Oncol 121:317–319PubMedCrossRef

Takenoshita S, Matsuzaki S, Nakano G-I, Kimura H, Hoshi H, Shoda H, Nakamura T (1984) Selective elevation of the N ¹-acetylspermidine level in human colorectal adenocarcinomas. Cancer Res 44:845–847PubMed

Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer DL, Janne J, Porter CW (2000) Effects of conditional overexpression of spermidine/spermine N¹-acetyltransferase on polyamine pool dynamics, cell growth, and sensitivity to polyamine analogs. J Biol Chem 275:38319–38328PubMedCrossRef

Wallace HM, Duthie J, Evans DM, Lamond S, Nicoll KM, Heys SD (2000) Alterations in polyamine catabolic enzymes in human breast cancer tissue. Clin Cancer Res 6:3657–3661PubMed

Titel: Increase of N 1 ,N 12-diacetylspermine in tissues from colorectal cancer and its liver metastasis
verfasst von: Go Kuwata
Kyoko Hiramatsu
Keijiro Samejima
Kaori Iwasaki
Kei-ichi Takahashi
Koichi Koizumi
Shin-ichiro Horiguchi
Shun-suke Moriya
Masaki Kobayashi
Masao Kawakita
Publikationsdatum: 01.06.2013
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-013-1405-5

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Increase of N ¹ ,N ¹²-diacetylspermine in tissues from colorectal cancer and its liver metastasis