TITLE

Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice

AUTHOR(S)
Sansom, Owen J.; Mansergh, Fiona C.; Evans, Martin J.; Wilkins, Julie A.; Clarke, Alan R.
PUB. DATE
October 2007
SOURCE
Gut;Oct2007, Vol. 56 Issue 10, p1410
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: SPARC (secreted protein acidic, rich in cysteine) is a matricellular protein that has been found to be activated in a number of human cancers. More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo. Methods: SPARC upregulation was determined in intestinal adenomas of tumour-prone ApcMin/+ mice at both the RNA and the protein level. To determine the functional importance of SPARC for intestinal tumorigenesis we then intercrossed Sparc knockout mice with ApcMin/+ mice (n = 20). Intestinal enterocyte migration was examined using bromodeoxyuridine labelling studies. Results: Levels of murine Sparc and several related proteins were upregulated in adenomas arising in ApcMin/+mice. A deficiency of Sparc strongly suppressed adenomo formation in ApcMin/+ mice (p⩾0.001). Importantly, a deficiency of Sparc also accelerated enterocyte migration (p = 0.01), as perturbed slow epithelial migration may underpin adenoma formation in the intestine. Conclusions: These data implicate Sparc in both cell migration and tumour formation, and identify Sparc as a potential therapeutic target for colorectal cancer.
ACCESSION #
27148473

 

Related Articles

  • Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas. Re, E C del; Shuja, S; Cai, J; Murnane, M J // British Journal of Cancer;4/1/2000, Vol. 82 Issue 7, p1317 

    Our analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in...

  • Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer. Herszényi, László; Farinati, Fabio; Cardin, Romilda; István, Gábor; Molnár, László D.; Hritz, István; De Paoli, Massimo; Plebani, Mario; Tulassay, Zsolt // BMC Cancer;2008, Vol. 8, Special section p1 

    Background: Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer invasion. The tumor marker utility and prognostic relevance of these proteases have not been evaluated in the same experimental setting and...

  • Laparoscopic radiofrequency of hepatocellular carcinoma using ultrasound-guided selective intrahepatic vascular occlusion. Santambrogio, R.; Costa, M.; Barabino, M.; Opocher, E. // Surgical Endoscopy;Sep2008, Vol. 22 Issue 9, p2051 

    The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. The authors aimed to assess a novel operative combination of laparoscopic radiofrequency (LRF) with a selective intrahepatic vascular occlusion...

  • SERRATED PATHWAY COLORECTAL CANCER IN THE POPULATION: GENETIC CONSIDERATION. Young, Joanne; Jenkins, Mark; Parry, Susan; Young, Bruce; Nancarrow, Derek; English, Dallas; Giles, Graham; Jass, Jeremy // Gut;Oct2007, Vol. 56 Issue 10, p1453 

    The article explores the evidence of the development of advanced serrated polyps. It has been found that it is a genetic trait with implications for colorectal cancer and prevention in the wider population. One of the most important seeds for this change has been the recognition of a serrated...

  • Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini. Thewarach Laha; Paul Brindley; Alex Loukas // Parasitology Research;Mar2008, Vol. 102 Issue 4, p757 

    Abstract  Protease activities in extracts of Opisthorchis viverrini were investigated using gelatin zymography and fluorogenic peptide substrates. Using gelatin-impregnated X-ray film, 2 μg of O. viverrini excretory–secretory products (Ov-ES) and adult...

  • Diethanolamine Induces Hepatic Choline Deficiency in Mice. Lehman-McKeeman, Lois D.; Gamsky, Elizabeth A.; Hicks, Sarah M.; Vassallo, Jeffrey D.; Mar, Mei-Heng; Zeisel, Steven H. // Toxicological Sciences;May2002, Vol. 67 Issue 1, p38 

    The purpose of the present experiments was to test the hypothesis that diethanolamine (DEA), an alkanolamine shown to be hepatocarcinogenic in mice, induces hepatic choline deficiency and to determine whether altered choline homeostasis was causally related to the carcinogenic outcome. To...

  • Expression of cystatin C in clinical human colorectal cancer tissues. Saleh, Yousif; Sebzda, Tadeusz; Warwas, Maria; Kopec, Wieslaw; Ziólkowska, Jolanta; Siewinski, Maciej // Journal of Experimental Therapeutics & Oncology;2005, Vol. 5 Issue 1, p49 

    We studied the relation between the antipapain activity of cysteine proteinase inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti-chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour tissues immunoperoxidase reactivity was present in the...

  • Reply to Dr. Kountouras et al. van der Woude, C. J.; Moshage, H. // Apoptosis;Sep2004, Vol. 9 Issue 5, p659 

    The article presents a reply to Dr. Jannis Kountouras and his colleagues about their research on cancer patients. The pathogenesis of cancer in chronic ulcerative colitis (UC) is poorly understood, although there are indications that this pathogenesis is different from that of sporadic cancer:...

  • Current directions in chemotherapy for colorectal cancer. Inoue, Yasuhiro; Miki, Chikao; Kusunoki, Masato // Journal of Gastroenterology;Sep2006, Vol. 41 Issue 9, p821 

    The article discusses the conceptual revolution of cancer chemotherapy in patients with colorectal cancer. The proper use of treatment options like combination therapy, preference of agents for first-line treatment, oral fluoropyrimidines and combination of local therapies are offered. The...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics