Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
June-2017 Volume 37 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 37 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells

  • Authors:
    • M. Waheed Roomi
    • Tatiana Kalinovsky
    • Aleksandra Niedzwiecki
    • Matthias Rath
  • View Affiliations / Copyright

    Affiliations: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA
  • Pages: 3681-3687
    |
    Published online on: April 24, 2017
       https://doi.org/10.3892/or.2017.5597
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Melanoma, an extremely aggressive cancer, causes the most skin cancer-related deaths, due to metastasis to other areas of the body, such as lymph nodes, lungs, liver, brain or bone. It is characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix and basement membrane, allowing cancer cells to spread to distal organs. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in regulation of MMP-2 and -9 in human melanoma A-2058 cells. Human A-2058 cells were grown in DMEM supplemented with 15% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed with PBS and incubated in serum-free media with phorbol 12-myristate 13-acetate (PMA) at 10, 25, 50 and 100 ng/ml; TNF-α and IL-1β at 0.1, 1, 10 and 25 ng/ml; LPS at 10, 25, 50 and 100 µg/ml; epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10, 25, 50 and 100 µM without and with PMA; a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract without and with PMA at 10, 50, 100, 500 and 1,000 µg/ml; actinomycin D and cyclohexamide at 2 and 4 µM; retinoic acid and dexamethasone at 50 µM. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by zymography and densitometry. Melanoma A-2058 demonstrated strong expression of MMP-2 and slight expression of MMP-9. PMA at 100 ng/ml showed no effect on MMP-2 secretion but potently upregulated MMP-9 secretion to 400% that of control. TNF-α showed no significant overall effect on expression of MMP-2 but potent dose-dependent increased MMP-9 secretion with 200% of control at 25 ng/ml. IL-1β showed no significant effect on MMP-2 or MMP-9 secretion by A-2058 cells, except at 25 ng/ml where MMP-2 level was reduced by ~40% and MMP-9 secretion ~50%. LPS treatment showed no significant effect on MMP-2 secretion and enhanced MMP-9 secretion up to 25 µg/ml followed by decreased level. EGCG, NM and doxycycline, without and with PMA, downregulated the expression of MMP-2 and MMP-9 in a dose-dependent manner. Actinomycin D, cyclohexamide and retinoic acid had inhibitory effects on MMP-2, while dexamethasone showed slight stimulatory effect on MMP-2 secretion. Our results showed that select cytokines, mitogens and inhibitors modulated A-2058 MMP-2 and MMP-9 expression. They suggest the clinical potential of MMP inhibitors, especially the non-toxic ones, such as the nutrient mixture and its component EGCG in management of melanoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

ACS: Key statistics for melanoma skin cancer. http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statisticsLast revised: 05/20/2016. 12 /12–/16

2 

Yurchenco PD and Schittny JC: Molecular architecture of basement membranes. FASEB J. 4:1577–1590. 1990.PubMed/NCBI

3 

Barsky SH, Siegal GP, Jannotta F and Liotta LA: Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab Invest. 49:140–147. 1983.PubMed/NCBI

4 

Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM and Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 284:67–68. 1980. View Article : Google Scholar : PubMed/NCBI

5 

Nikkola J, Vihinen P, Vuoristo MS, Kellokumpu-Lehtinen P, Kähäri VM and Pyrhönen S: High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma. Clin Cancer Res. 11:5158–5166. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Malaponte G, Zacchia A, Bevelacqua Y, Marconi A, Perrotta R, Mazzarino MC, Cardile V and Stivala F: Co-regulated expression of matrix metalloproteinase-2 and transforming growth factor-β in melanoma development and progression. Oncol Rep. 24:81–87. 2010. View Article : Google Scholar : PubMed/NCBI

7 

de Visser KE and Coussens LM: The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol. 13:118–137. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Qin Y, Ekmekcioglu S, Liu P, Duncan LM, Lizée G, Poindexter N and Grimm EA: Constitutive aberrant endogenous interleukin-1 facilitates inflammation and growth in human melanoma. Mol Cancer Res. 9:1537–1550. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Niedzwiecki A, Roomi MW, Kalinovsky T and Rath M: Micronutrient synergy: a new tool in effective control of metastasis and other key mechanisms of cancer. Cancer Metastasis Rev. 29:529–542. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Rath M and Pauling L: Plasmin-induced proteolysis and the role of apoprotein(a), lysine and synthetic analogs. Orthomolecular Med. 7:17–23. 1992.

13 

Sun Z, Chen YH, Wang P, Zhang J, Gurewich V, Zhang P and Liu JN: The blockage of the high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochim Biophys Acta. 1596:182–192. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Mussini E, Hutton JJ Jr and Udenfriend S: Collagen proline hydroxylase in wound healing, granuloma formation, scurvy, and growth. Science. 157:927–929. 1967. View Article : Google Scholar : PubMed/NCBI

15 

Kivirikko KI and Myllylä R: Collagen glycosyltransferases. Int Rev Connect Tissue Res. 8:23–72. 1979. View Article : Google Scholar : PubMed/NCBI

16 

Valcic S, Timmermann BN, Alberts DS, Wächter GA, Krutzsch M, Wymer J and Guillén JM: Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 7:461–468. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Mukhtar H and Ahmad N: Tea polyphenols: Prevention of cancer and optimizing health. Am J Clin Nutr. 71 Suppl:1698S–1702S, discussion 1703S-1704S. 2000.PubMed/NCBI

18 

Yang GY, Liao J, Kim K, Yurkow EJ and Yang CS: Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 19:611–616. 1998. View Article : Google Scholar : PubMed/NCBI

19 

Taniguchi S, Fujiki H, Kobayashi H, Go H, Miyado K, Sadano H and Shimokawa R: Effect of (−)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. Cancer Lett. 65:51–54. 1992. View Article : Google Scholar : PubMed/NCBI

20 

Hara Y: Green tea: Health Benefits and Applications. Marcel Dekker; New York, Basel: 2001, https://doi.org/10.1201/9780203907993 View Article : Google Scholar

21 

Gupta S, Hastak K, Afaq F, Ahmad N and Mukhtar H: Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of nuclear factor kappa B and induction of apoptosis. Oncogene. 23:2507–2522. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Fujiki H, Suganuma M, Okabe S, Sueoka E, Suga K, Imai K, Nakachi K and Kimura S: Mechanistic findings of green tea as cancer preventive for humans. Proc Soc Exp Biol Med. 220:pp. 225–228. 1999; View Article : Google Scholar : PubMed/NCBI

23 

Kawakami S, Kageyama Y, Fujii Y, Kihara K and Oshima H: Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells. Anticancer Res. 21:213–219. 2001.PubMed/NCBI

24 

Morini M, Cai T, Aluigi MG, Noonan DM, Masiello L, De Flora S, DAgostini F, Albini A and Fassina G: The role of the thiol N-acetylcysteine in the prevention of tumor invasion and angiogenesis. Int J Biol Markers. 14:268–271. 1999.PubMed/NCBI

25 

Yoon SO, Kim MM and Chung AS: Inhibitory effect of selenite on invasion of HT1080 tumor cells. J Biol Chem. 276:20085–20092. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Cha J, Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A and Rath M: Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int J Oncol. 42:55–64. 2013.PubMed/NCBI

27 

Naidu KA, Karl RC, Naidu KA and Coppola D: Antiproliferative and proapoptotic effect of ascorbyl stearate in human pancreatic cancer cells: Association with decreased expression of insulin-like growth factor 1 receptor. Dig Dis Sci. 48:230–237. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Anthony HM and Schorah CJ: Severe hypovitaminosis C in lung-cancer patients: The utilization of vitamin C in surgical repair and lymphocyte-related host resistance. Br J Cancer. 46:354–367. 1982. View Article : Google Scholar : PubMed/NCBI

29 

Maramag C, Menon M, Balaji KC, Reddy PG and Laxmanan S: Effect of vitamin C on prostate cancer cells in vitro: Effect on cell number, viability, and DNA synthesis. Prostate. 32:188–195. 1997. View Article : Google Scholar : PubMed/NCBI

30 

Koh WS, Lee SJ, Lee H, Park C, Park MH, Kim WS, Yoon SS, Park K, Hong SI, Chung MH, et al: Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. Anticancer Res. 18:2487–2493. 1998.PubMed/NCBI

31 

Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E and Levine M: Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 102:pp. 13604–13609. 2005; View Article : Google Scholar : PubMed/NCBI

32 

Núñez Martín C, de Apodaca y Ruiz A Ortiz and Ruiz A: Ascorbic acid in the plasma and blood cells of women with breast cancer. The effect of the consumption of food with an elevated content of this vitamin. Nutr Hosp. 10:368–372. 1995.(In Spanish).

33 

Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D and Bruckner HW: Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 103:183–189. 1996. View Article : Google Scholar : PubMed/NCBI

34 

Cooke JP and Dzau VJ: Nitric oxide synthase: Role in the genesis of vascular disease. Annu Rev Med. 48:489–509. 1997. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Roomi MW, Kalinovsky T, Niedzwiecki A and Rath M: Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells. Oncol Rep 37: 3681-3687, 2017.
APA
Roomi, M.W., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2017). Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells. Oncology Reports, 37, 3681-3687. https://doi.org/10.3892/or.2017.5597
MLA
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells". Oncology Reports 37.6 (2017): 3681-3687.
Chicago
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells". Oncology Reports 37, no. 6 (2017): 3681-3687. https://doi.org/10.3892/or.2017.5597
Copy and paste a formatted citation
x
Spandidos Publications style
Roomi MW, Kalinovsky T, Niedzwiecki A and Rath M: Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells. Oncol Rep 37: 3681-3687, 2017.
APA
Roomi, M.W., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2017). Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells. Oncology Reports, 37, 3681-3687. https://doi.org/10.3892/or.2017.5597
MLA
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells". Oncology Reports 37.6 (2017): 3681-3687.
Chicago
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells". Oncology Reports 37, no. 6 (2017): 3681-3687. https://doi.org/10.3892/or.2017.5597
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team