Expression analysis of matrix metalloproteinase-13 in human gastric cancer in the presence of Helicobacter Pylori infection

Abstract

BACKGROUND:

Matrix metalloproteinases (MMPs) can degrade essentially the extracellular matrix (ECM) components. MMPs are important regulators of tumor growth; hence the enzymes are considered as important targets for cancer therapy.MMP-13 is specially activated in gastric cancer and promotes the invasiveness of the primary tumors. Helicobacter Pylori (H.pylori) interacts with gastric epithelial cells and stimulates it to produce MMP-13 in vitro.

OBJECTIVE:

The relation between MMP-13 gene expression and clinicopathological characteristics of gastric cancer in the presence of H.pylori infection was investigated in fifty patients.

METHODS:

The level of MMP-13 gene expression was measured by quantitative Real-time PCR method and was evaluated between two groups of normal and carcinomatous tissues.

RESULTS:

The results showed 30% elevation of MMP-13 expression in tumor tissues.H.pylori infection did not have a significant effect on the expression of MMP-13. There was a correlation between gene expression and tumor type (P value = 0.032). In addition, there was a significant correlation between MMP-13 gene expression and tumor stage in intestinal group (P value = 0.023).

CONCLUSIONS:

Based on the results, it might be concluded that in intestinal group, immune system plays an important role in reducing gene expression. Results also showed over expression (60%) in diffuse group. These findings suggest that using MMP-13 inhibitors in diffuse group might contribute to the control of tumor growth.

Keywords

gastric cancer Helicobacter Pylori real-time PCR

References

Elnemr

, Bandou

, Kinoshita

, Kawamura

, Takahashi

, Tochiori

, Endou

and Sasaki

, Expression of Collagenase-3 (matrix metalloproteinase-13) in Human Gastric Cancer. Gastric Cancer. 2003; 6(1): 30-8.

Elnemr

, Yonemura

, Bandou

, Kinoshita

, Kawamura

, Takahashi

, Tochiori

, Endou

and Sasaki

, Expression of collagenase-3 matrix metalloproteinase-13 in human gastric cancer. Gastric Cancer. 2003; 6: 30-38.

Dicken

B.J.

, Bigam

D.L.

, Cass

, Mackey

J.R.

, Joy

A.A.

and Hamilton

S.M.

, Gastric Adenocarcinoma. Ann Surg. 2005 Jan; 241(1): 27-39.

Fenogilo-Preiser

, Carneiro

, Correa

, et al. Gastric carcinoma. In: Hamilton S, Aaltonin L, eds. Pathology and Genetics. Tumors of the Digestive System, vol. 1. Lyon, France: Lyon Press 2000; 37-52.

van der Woude

C.J.

, Kleibeuker

J.H.

, Tiebosch

A.T.G.M.

, Homan

, Beuving

, Jansen

P.L.M.

and Moshage

, Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins. J ClinPathol. 2003 Sep; 56(9): 699-702.

Stadtlander

C.T.H.

, Molecular epidemiology, pathogenesis and prevention of gastric cancer. Carcinogenesis. 1999; 20: 2195-208.

Forman

, Newell

D.G.

, Fullerton

, et al. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991; 302: 1302-1305.

Forman

, Burley

, Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract Res ClinGastroenterol. 2006; 20: 633-49.

Etoh

, Inoue

, Yoshikawa

, Barnard

G.F.

, Kitano

and Mori

, Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness, Gut. 2000; 47: 50-6.

10.

Ozen

, Dinler

, Akyn

, et al. Helicobacter pylori infection and recurrent abdominal pain in Turkish children. Helicobacter. 2001; 6(3): 234-8.

11.

Welgus

H.G.

, Kobayashi

D.K.

and Jeffrey

J.J.

, The collagen substrate specificity of rat uterus collagenase. J Biol Chem. 1983; 258(23): 14162-14165.

12.

Hsu

C.P.

, Shen

G.H.

and Ko

J.L.

, Matrix Metalloproteinase-13 Expression Is Associated with Bone Marrow Microinvolvement and Prognosis in Non-small Cell Lung Cancer. Lung Cancer. 2006; 52(3): 349-57.

13.

http://www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-staging.

14.

International Agency for Research on Cancer. Schistosomes, liver flukes and Helicobacter pylori. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 1994; 61: 1-241.

15.

Faivre

, Benhamiche

, Gastric carcinoma: new developments in the field. Gastroenterology. 1995; 90: 2213-2216.

16.

Parsonnet

, Friedman

G.D.

, Vandersteen

D.P.

, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991; 325: 1127-1131.

17.

Johansson

, Vaalamo

, Grénman

, Hietanen

, Klemi

, Saarialho-Kere

, and Kähäri

V.M.

, Collagenase-3 (MMP-13) is Expressed by Tumor Cells in Invasive Vulvar Squamous Cell Carcinomas. Am J Pathol. 1999; 154(2): 469-80.

18.

Uria

JA.

, Balbin

, Lopez

JM.

, Alvarez

, Vizoso

, Takigawa

and Lopez-Otin

, Collagenase-3 (MMP-13) expression in squamous cell carcinomas of the head and neck. Am J Pathol. 1998; 153: 91-101.

19.

Freije

JM.

, Diez-Itza

, Balbin

, Sanchez

LM.

, Blasco

, Tolivia

and Lopez-Otin

, Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem. 1994; 269(24): 16766-16773.

20.

Ashorn

, Maki

, Hallstrm

, et al. Helicobacter pylori infection in Finnish children and adolescents. Scand J Gastroenterol. 1995; 30(9): 876-9.

21.

Gooz

, Shaker

, Gooz

and Smolka

A.J.

, Interleukin 1β induces gastric epithelial cell matrix metalloproteinase secretion and activation during Helicobacter pylori infection. Gut. 2003; 52: 1250-1256.

22.

Gööz

, Gööz

and Smolka

A.J.

, Epithelial and bacterial metalloproteinases and their inhibitors in H. pylori infection of human gastric cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2001; 281: G823-G832.

23.

Nouraie

, Latifi-Navid

, Rezvan

, et al. Childhood hygienic practice and family education status determine the prevalence of Helicobacter pylori infection in Iran. Helicobacter. 2009; 14(1): 40-6.

24.

Rostami

, Kadivar

, Aznab

and Abachi

, Influence of age and gender on association between-765G> C COX-2 genetic polymorphism and gastric adenocarcinoma risk: a case-control study in Iran. GastroenterolHepatol Bed Bench. 2011; 5: 29-3.

25.

Leeman

M.F.

, McKay

J.A.

and Murray

G.I.

, Matrix Metalloproteinase-13 Activity Is Associated with Poor Prognosis in Colorectal Cancer. J Clin Pathol. 2002; 55(10): 758-62.

26.

Pillinger

M.H.

, Marjanovic

, Kim

S.Y.

, Scher

J.U.

, Izmirly

, Tolani

, Dinsell

, Lee

Y.C.

, Blaser

M.J.

and Abramson

S.B.

, Matrix Metalloproteinase Secretion by Gastric Epithelial Cells Is Regulated by E Prostaglandins and MAPKs, The American Society for Biochemistry and Molecular Biology, Inc. 2004.

27.

Blaser

M.J.

and Atherton

J.C.

, Helicobacter pylori persistence: biology and disease. J. Clin. Investig. 2004; 113: 321-333.

28.

Smith

M.G.

, Hold

G.L.

, Tahara

and El-Omar

E.M.

, Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006; 12: 2979-90.

29.

McLean

M.H.

and El-Omar

E.M.

, Genetics of gastric cancer. Nature Rev GastroenterolHepatol. 2014; 11: 664-74.

30.

Johansson

, Airola

, Grenman

, Kaineimi

A.L.

, Saarialho-Kere

and Kahari

V.M.

, Expression of collagenase-3 (matrix metalloproteinase-13) in squamous cell carcinomas of the headand neck. Am J Pathol. 1997; 151: 499-508.

31.

Correa

P.A.

, Human model of gastric carcinogenesis. Cancer Res. 1988; 48: 3554-60.

32.

Bostrom

PJ.

, Ravanti

, Reunanen

, Aaltonen

, Soderstrom

KO.

, Kahari

VM.

and Laato

, Expression of collagenase-3 (matrix metalloproteinase-13) in transitional-cell carcinoma of the urinary bladder. Int J Cancer. 2000; 88: 417-23.

33.

Barooei

, Mahmoudian

R.A.

, Abbaszadegan

M.R.

, Mansouri

and Gholamin

, Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer. Med Oncol. 2015; 32: 217.

34.

Malekzadeh

, Derakhshan

M.H.

and Malekzadeh

, Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009; 12: 576-83.

35.

Rad

, Dossumbekova

, Neu

, Lang

, Bauer

, Saur

, et al. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut. 2004; 53: 1082-9.

36.

Peek

R.M.

, Jr. Miller

G.G.

, Tham

K.T.

, Perez-Perez

G.I.

, Zhao

, Atherton

J.C.

and Blaser

M.J.

, Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab. Investig. 1995; 73: 760-770.

37.

Katoh

, Nagata

, Kuroda

, et al. Glutathione S-transferase M1(GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis. 1996; 17: 1855-9.

38.

Uitto

V.J.

, Airola

, Vaalamo

, Johansson

, Putnins

E.E.

, Firth

J.D.

, et al. Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation. Am J Pathol. 1998; 152: 1489-99.

39.

Setiawan

V.W.

, Zhang

Z.F.

, Yu

G.P.

, et al. GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population. Cancer Epidemiol Biomarkers Prev. 2000; 9: 73-80.

40.

Bin

, et al. Tumor-derived Matrix Metalloproteinase-13 (MMP-13) Correlates with Poor Prognoses of Invasive Breast Cancer, BMC Cancer. 2008; 8(83).

41.

Kaposztas

, Kalmar

, Cseke

, Illenyi

, Kelemen

and Horvath

O.P.

, rognostic factors in the surgical treatment of gastric cancer - 10 years experience. MagySeb. 2007; 60: 71-8.