Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Diagnosis & Therapy
Published in: Molecular Diagnosis & Therapy 3/2007

01-05-2007 | Original Research Article

Relationship between Matrix Metalloproteinase 2 and Lung Cancer Progression

Authors: Chun-Bao Guo, Dr Shan Wang, Chun Deng, Dian-Liang Zhang, Fu-Ling Wang, Xian-Qing Jin

Published in: Molecular Diagnosis & Therapy | Issue 3/2007

Login to get access

Abstract

Background and objective: Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. MMP2 and MMP9 have previously been implicated in lymphatic and vascular invasion of lung cancer; however, the expression and prognostic significance of MMP2 and MMP9 is not fully clarified. This study was designed to investigate the significance of MMP2 and MMP9 in lung cancer tissue or serum, and their correlation with lung cancer prognosis.
Methods: Immunohistochemical analysis was performed to determine MMP2 and MMP9 staining in human nonsmall cell lung cancer (NSCLC). Serum MMP2 and MMP9 protein levels in patients after surgery were measured using the ELISA method. The correlation between MMP2 and MMP9 serum levels and clinicopathological features of NSCLC were analyzed by survival analysis. We also performed reverse transcriptase (RT)-PCR assays to detect messenger RNA (mRNA) expression to further confirm the activity of MMP2 and MMP9 in human lung cancer.
Results: Increased MMP2 immunostaining and MMP2 serum level correlated with advanced tumor stage and the presence of distant metastasis (Pearson’s χ2 test and ANOVA, p < 0.05). However, for MMP9, only serum level showed a correlation with advanced tumor stage. No significant correlation was observed between MMP2 or MMP9 immunostaining expression and tumor histologic features (Pearson’s χ2 test, p = 0.061 and p = 0.087, respectively). A high densitometry value of MMP2 and MMP9 PCR products (i.e. mRNA expression level) was related to poor differentiation grade, distant metastasis, and small cell carcinoma histologic type (ANOVA, p < 0.05).
Conclusions: Our results suggest that MMP2 is a more sensitive predictor than MMP9 of lung cancer progression, metastasis, and survival. Serum MMP2 levels may be a valuable prognosis variable and could help to stratify lung cancer patients into low- and high-risk groups.
Literature
1.
Vihinen P, Kahari VM. Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 2002; 99: 157–66PubMedCrossRef
2.
Bergman B, Brezicka FT, Engstrom CP, et al. Clinical usefulness of serum assays of neuron-specific enolase, carcinoembryonic antigen and CA-50 antigen in the diagnosis of lung cancer. Eur J Cancer 1993; 29A(2): 198–202PubMedCrossRef
3.
Niho S, Nishiwaki Y, Goto K, et al. Significance of serum pro-gastrin-releasing peptide as a predictor of relapse of small cell lung cancer: comparative evaluation with neuron-specific enolase and carcinoembryonic antigen. Lung Cancer 2000; 27(3): 159–67PubMedCrossRef
4.
Schneider J, Philipp M, Velcovsky HG, et al. Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19-fragments (CYFRA 21-1) in patients with lung cancer in comparison to other lung diseases. Anticancer Res 2003; 23(2A): 885–93PubMed
5.
Nilsson O, Johansson C, Glimelius B, et al. Sensitivity and specificity of CA242 in gastro-intestinal cancer: a comparison with CEA, CA50 and CA 19-9. Br J Cancer 1992; 65(2): 215–21PubMedCrossRef
6.
Birim O, Kappetein AP, Takkenberg JJ, et al. Survival after pathological stage IA nonsmall cell lung cancer: tumor size matters. Ann Thorac Surg 2005; 79: 1137–41PubMedCrossRef
7.
Brinckerhoff CE, Rutter JL, Benbow U. Interstitial collagenases as markers of tumor progression. Clin Cancer Res 2000; 6: 4823–30PubMed
8.
Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999; 13: 781–92PubMed
9.
Tsunezuka Y, Kinoh H, Takino T, et al. Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Res 1996; 56: 5678–83PubMed
10.
Cai M, Onoda K, Takao M, et al. Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer. Clin Cancer Res 2002; 8: 1152–6PubMed
11.
Zinzindohoue F, Lecomte T, Ferraz JM, et al. Prognostic significance of MMP-1 and MMP-3 functional promoter polymorphisms in colorectal cancer. Clin Cancer Res 2005; 11: 594–9PubMed
12.
Fang S, Jin X, Wang R, et al. Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China. Carcinogenesis 2005; 26: 481–6PubMedCrossRef
13.
Yu C, Zhou Y, Miao X, et al. Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. Cancer Res 2004; 64: 7622–8PubMedCrossRef
14.
Kanamori Y, Matsushima M, Minaguchi T, et al. Correlation between expression of the matrix metalloproteinase-1 gene in ovarian cancers and an insertion/ deletion polymorphism in its promoter region. Cancer Res 1999; 59: 4225–7PubMed
15.
Leppa S, Saarto T, Vehmanen L, et al. A high serum matrix metalloproteinase-2 level is associated with an adverse prognosis in node-positive breast carcinoma. Clin Cancer Res 2004; 10(3): 1057–63PubMedCrossRef
16.
Sheen-Chen SM, Chen HS, Eng HL, et al. Serum levels of matrix metalloproteinase 2 in patients with breast cancer. Cancer Lett 2001; 173(1): 79–82PubMedCrossRef
17.
Moser PL, Hefler L, Tempfer C, et al. Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage I and II endometrial cancer. Anticancer Res 1999; 19(3B): 2365–7PubMed
18.
Sier CF, Casetta G, Verheijen JH, et al. Enhanced urinary gelatinase activities (matrix metalloproteinases 2 and 9) are associated with early-stage bladder carcinoma: a comparison with clinically used tumor markers. Clin Cancer Res 2000; 6(6): 2333–40PubMed
19.
Ueno H, Nakamura H, Inoue M, et al. Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 1997; 57: 2055–60PubMed
20.
Hanke B, Wein A, Martus P, et al. Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy. Br J Cancer 2003; 88: 1248–50PubMedCrossRef
21.
Sobin LH, Wittekind C. TNM classification of malignant tumors. 5th ed. New York: Wiley-Leiss, 1997
22.
Ross JS, Kallakury BV, Sheehan CE, et al. Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence. Clin Cancer Res 2004; 10: 2466–72PubMedCrossRef
23.
Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 2003; 200(4): 448–64PubMedCrossRef
24.
Passlick B, Sienel W, Seen-Hibler R, et al. Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer. Clin Cancer Res 2000; 6: 3944–8PubMed
25.
Gonzalez-Avila G, Iturria C, Vadillo F, et al. 72-kD (MMP2) and 92-kD (MMP9) type IV collagenase production and activity in different histologic types of lung cancer cells. Pathobiology 1998; 66: 5–16PubMedCrossRef
26.
Luca M, Huang S, Gershenwald JE, et al. Expression of interleukin-8 by human melanoma cells up-regulates MMP2 activity and increases tumor growth and metastasis. Am J Pathol 1997; 151: 1105–13PubMed
27.
Brown PD, Bloxidge RE, Stuart NS, et al. Association between expression of activated 72-kilodalton gelatinase and tumor spread in non-small-cell lung carcinoma. J Natl Cancer Inst 1993; 85(7): 574–8PubMedCrossRef
28.
Ishikawa S, Takenaka K, Yanagihara K, et al. Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer. Clin Cancer Res 2004; 10(19): 6579–85PubMedCrossRef
29.
Liao J, Wolfman JC, Wolfman A. K-ras regulates the steady-state expression of matrix metalloproteinase 2 in fibroblasts. J Biol Chem 2003; 278(34): 31871–8PubMedCrossRef
30.
Pinto CA, Carvalho PE, Antonangelo L, et al. Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung. Clin Cancer Res 2003; 9(8): 3098–104PubMed
31.
Iizasa T, Fujisawa T, Suzuki M, et al. Elevated levels of circulating plasma matrix metalloproteinase 9 in nonsmall cell lung cancer patients. Clin Cancer Res 1999; 5: 149–53PubMed
32.
Ylisirnio S, Hoyhtya M, Turpeenniemi-Hujanen T. Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer: TIMP-1 as a prognostic marker. Anticancer Res 2000; 20: 1311–6PubMed
33.
Price SJ, Greaves DR, Watkins H. Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 2001; 276: 7549–58PubMedCrossRef
34.
Wurtz SO, Christensen IJ, Schrohl AS, et al. Measurement of the uncomplexed fraction of tissue inhibitor of metalloproteinases-1 in the prognostic evaluation of primary breast cancer patients. Mol Cell Proteomics 2005; 4: 483–91PubMedCrossRef
35.
Lehti K, Valtanen H, Wickstrom SA, et al. Regulation of membrane-type-1 matrix metalloproteinase activity by its cytoplasmic domain [published erratum appears in J Biol Chem 2004; 279 (38): 40246]. J Biol Chem 2000 May 19; 275(20): 15006–13PubMedCrossRef
36.
Shou Y, Hirano T, Gong Y, et al. Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer. Br J Cancer 2001; 85: 1706–12PubMedCrossRef
37.
Farias E, Ranuncolo S, Cresta C, et al. Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients. Int J Cancer 2000; 89: 389–94PubMedCrossRef
38.
Chen JJ, Peck K, Hong TM, et al. Global analysis of gene expression in invasion by a lung cancer model. Cancer Res 2001; 61: 5223–30PubMed
39.
Su JM, Wei YQ, Tian L, et al. Active immunogene therapy of cancer with vaccine on the basis of chicken homologous matrix metalloproteinase-2. Cancer Res 2003; 63: 600–7PubMed
40.
Shan B, Zhuo Y, Chin D, et al. Cyclin-dependent kinase 9 is required for tumor necrosis factor-alpha-stimulated matrix metalloproteinase-9 expression in human lung adenocarcinoma cells. J Biol Chem 2005; 280: 1103–11PubMedCrossRef
Metadata
Title
Relationship between Matrix Metalloproteinase 2 and Lung Cancer Progression
Authors
Chun-Bao Guo
Dr Shan Wang
Chun Deng
Dian-Liang Zhang
Fu-Ling Wang
Xian-Qing Jin
Publication date
01-05-2007
Publisher
Springer International Publishing
Published in
Molecular Diagnosis & Therapy / Issue 3/2007
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI
https://doi.org/10.1007/BF03256240

Other articles of this Issue 3/2007

Molecular Diagnosis & Therapy 3/2007 Go to the issue

Short Communication

Transforming Growth Factor β-1 −509C>T Polymorphism in Indian Patients with Primary Open Angle Glaucoma

Cancer

Management Updates for Women with a BRCA1 or BRCA2 Mutation

Short Communication

Assessment of Human Serotonin 1A Receptor Polymorphisms and SSRI Responsiveness

Original Research Article

Impact of CYP2D6 Genetic Polymorphism on Tramadol Pharmacokinetics and Pharmacodynamics

Original Research Article

The Pharmacogenetics of Lithium Response Depends upon Clinical Co-Morbidity

Technical Resource

DGEM — A Microarray Gene Expression Database for Primary Human Disease Tissues
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits