Skip to main content
Erschienen in: Digestive Diseases and Sciences 11/2011

01.11.2011 | Original Article

Expression of ADAMTS12 in Colorectal Cancer-Associated Stroma Prevents Cancer Development and Is a Good Prognostic Indicator of Colorectal Cancer

verfasst von: Da Wang, Tao Zhu, Fu-Biao Zhang, Chao He

Erschienen in: Digestive Diseases and Sciences | Ausgabe 11/2011

Einloggen, um Zugang zu erhalten

Abstract

Aim

The aim of this study was to investigate the role of ADAMTS12 in colorectal cancer progression and to examine whether ADAMTS-12 can be considered as a prognostic indicator for colorectal cancer.

Methods

This study was performed on formalin-fixed paraffin-embedded resected specimens obtained from 112 patients with colorectal cancer. The expression level of ADAMTS12 was investigated by immunohistochemical staining to assess the relationship between ADAMTS12 expression and the clinicopathologic factors and to study the prognostic significance of ADAMTS12 in colorectal cancer patients.

Results

ADAMTS12 expression was mainly localized in the fibroblasts adjacent to the tumor cells or in macrophages in front of the invasive cancer margins. The ADAMTS12 expression was significantly correlated with the tumor histological grade, depth of tumor invasion, lymph node metastasis, and Dukes’ stage. Patients with low or no ADAMTS12 expression in the tumor stroma had a significantly poor overall survival or disease-free survival.

Conclusion

The expression of ADAMTS12 in colorectal cancer stroma plays an important role in inhibiting tumor development. Patients with ADAMTS12 expression showed better prognosis than those without ADAMTS12 expression. Thus, ADAMTS12 expression may be a good prognostic marker for colorectal cancer.
Literatur
2.
Zurück zum Zitat Freije JM, Balbin M, Pendas AM, Sanchez LM, Puente XS, Lopez-Otin C. Matrix metalloproteinases and tumor progression. Adv Exp Med Biol. 2003;532:91–107.PubMedCrossRef Freije JM, Balbin M, Pendas AM, Sanchez LM, Puente XS, Lopez-Otin C. Matrix metalloproteinases and tumor progression. Adv Exp Med Biol. 2003;532:91–107.PubMedCrossRef
3.
Zurück zum Zitat Illemann M, Bird N, Majeed A, et al. MMP-9 is differentially expressed in primary human colorectal adenocarcinomas and their metastases. Mol Cancer Res. 2006;4:293–302.PubMedCrossRef Illemann M, Bird N, Majeed A, et al. MMP-9 is differentially expressed in primary human colorectal adenocarcinomas and their metastases. Mol Cancer Res. 2006;4:293–302.PubMedCrossRef
4.
Zurück zum Zitat Apte SS. A disintegrin-like and metalloproteases (reprolysin type) with thrombospondin type 1 motifs: the ADAMTS family. Int J Biochem Cell Biol. 2004;36:981–985.PubMedCrossRef Apte SS. A disintegrin-like and metalloproteases (reprolysin type) with thrombospondin type 1 motifs: the ADAMTS family. Int J Biochem Cell Biol. 2004;36:981–985.PubMedCrossRef
5.
Zurück zum Zitat Cal S, Obaya AJ, Llamazares M, Garabaya C, Quesada V, Lopez-Otin C. Cloning, expression analysis, and tructural characterization of seven novel human DAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62.PubMedCrossRef Cal S, Obaya AJ, Llamazares M, Garabaya C, Quesada V, Lopez-Otin C. Cloning, expression analysis, and tructural characterization of seven novel human DAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62.PubMedCrossRef
6.
Zurück zum Zitat Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS etalloproteinases. Biochem J. 2005;386:15–27.PubMedCrossRef Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS etalloproteinases. Biochem J. 2005;386:15–27.PubMedCrossRef
7.
Zurück zum Zitat Balbin M, Fueyo A, Tester AM, et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet. 2003;35:252–257.PubMedCrossRef Balbin M, Fueyo A, Tester AM, et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet. 2003;35:252–257.PubMedCrossRef
8.
Zurück zum Zitat Lopez-Otin C, Matrisian LM. Emerging roles of proteases in tumour suppression. Nat Rev Cancer. 2007;7:800–808.PubMedCrossRef Lopez-Otin C, Matrisian LM. Emerging roles of proteases in tumour suppression. Nat Rev Cancer. 2007;7:800–808.PubMedCrossRef
9.
Zurück zum Zitat Lind GE, Kleivi K, Meling GI, et al. ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 2006;28:259–272.PubMed Lind GE, Kleivi K, Meling GI, et al. ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 2006;28:259–272.PubMed
10.
Zurück zum Zitat Dunn JR, Panutsopulos D, Shaw MW. METH-2 silencing and promoter hypermethylation in NSCLC. Br. J Cancer. 2004;91:1149–1154. Dunn JR, Panutsopulos D, Shaw MW. METH-2 silencing and promoter hypermethylation in NSCLC. Br. J Cancer. 2004;91:1149–1154.
11.
Zurück zum Zitat Lo PH, Leung AC, Kwok CY, et al. Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene. 2007;26:148–157.PubMedCrossRef Lo PH, Leung AC, Kwok CY, et al. Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene. 2007;26:148–157.PubMedCrossRef
12.
Zurück zum Zitat Jin H, Wang X, Ying J, et al. Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene. 2007;26:7490–7498.PubMedCrossRef Jin H, Wang X, Ying J, et al. Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene. 2007;26:7490–7498.PubMedCrossRef
13.
Zurück zum Zitat Cal S, Arguelles JM, Fernandez PL. and Lopez-Otin, C: Identification, characterization, and intracellular processing of ADAM-TS12, a novel human disintegrin with a complex structural organization involving multiple thrombospondin-1 repeats. J Biol Chem. 2001;276:17932–17940.PubMedCrossRef Cal S, Arguelles JM, Fernandez PL. and Lopez-Otin, C: Identification, characterization, and intracellular processing of ADAM-TS12, a novel human disintegrin with a complex structural organization involving multiple thrombospondin-1 repeats. J Biol Chem. 2001;276:17932–17940.PubMedCrossRef
14.
Zurück zum Zitat Liu CJ, Kong W, Xu K, et al. ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein. J Biol Chem. 2006;281:15800–15808.PubMedCrossRef Liu CJ, Kong W, Xu K, et al. ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein. J Biol Chem. 2006;281:15800–15808.PubMedCrossRef
15.
Zurück zum Zitat Llamazares M, Obaya AJ, Moncada-Pazos A, et al. The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signaling pathway. J. Cell ScI. 2007;120:3544–3552.CrossRef Llamazares M, Obaya AJ, Moncada-Pazos A, et al. The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signaling pathway. J. Cell ScI. 2007;120:3544–3552.CrossRef
16.
Zurück zum Zitat Moncada-Pazos A, Obaya AJ, Fraga MF, et al. The ADAMTS12 metalloprotease gene is epigenetically silenced in tumor cells and transcriptionally activated in the stroma during progression of colon cancer. J Cell Sci. 2009;15:2906–2913.CrossRef Moncada-Pazos A, Obaya AJ, Fraga MF, et al. The ADAMTS12 metalloprotease gene is epigenetically silenced in tumor cells and transcriptionally activated in the stroma during progression of colon cancer. J Cell Sci. 2009;15:2906–2913.CrossRef
17.
Zurück zum Zitat Zhou D, Pan G, Zheng C, Zheng J, Yian L, Teng X. Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues. BMC Cancer. 2008;8:353.PubMedCrossRef Zhou D, Pan G, Zheng C, Zheng J, Yian L, Teng X. Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues. BMC Cancer. 2008;8:353.PubMedCrossRef
18.
Metadaten
Titel
Expression of ADAMTS12 in Colorectal Cancer-Associated Stroma Prevents Cancer Development and Is a Good Prognostic Indicator of Colorectal Cancer
verfasst von
Da Wang
Tao Zhu
Fu-Biao Zhang
Chao He
Publikationsdatum
01.11.2011
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 11/2011
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-011-1723-x

Weitere Artikel der Ausgabe 11/2011

Digestive Diseases and Sciences 11/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.