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Article

Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts

  • Authors:
    • M. W. Roomi
    • T. Kalinovsky
    • M. Rath
    • A. Niedzwiecki
  • View Affiliations / Copyright

    Affiliations: Dr. Rath Research Institute, Santa Clara, CA 95050, USA
  • Pages: 1842-1848
    |
    Published online on: January 16, 2017
       https://doi.org/10.3892/or.2017.5368
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Abstract

Acute myeloid leukemia and head and neck squamous cell carcinomas are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in tumor invasion and metastasis. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in the regulation of MMP-2 and MMP-9 in human immortalized fibroblasts from FA. Human FA immortalized fibroblast cell lines FA-A:PD220 and FA-D2:PD20 were grown in minimum essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed with phosphate‑buffered saline (PBS) and incubated in serum-free media with the following: phorbol 12-myristate 13-acetate (PMA) at 10-100 ng/ml; tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) at 0.1-25 ng/ml; lipopolysaccharide (LPS) at 10-100 µg/ml; epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10-100 µM without and with PMA; a nutrient mixture (NM) without and with PMA at 10-1,000 µg/ml; actinomycin-D and cyclohexamide at 2 and 4 µM; retinoic acid and dexamethasone at 50 µM. After 24 h, media were removed and analyzed for MMP-2 and MMP-9 by zymography. Both FA cell lines expressed only MMP-2 and responded similarly to cytokines, mitogens, inducers and inhibitors. PMA potently stimulated MMP-9 and had a moderate effect on MMP-2. TNF-α showed variable effects on MMP-2 and significantly enhanced MMP-9. IL-1β enhanced MMP-2 slightly and MMP-9 significantly. LPS had a moderate stimulatory effect on MMP-2 and no effect on MMP-9. EGCG, Dox and NM, without and with PMA, downregulated MMP-2 and MMP-9 expression. Actinomycin-D, retinoic acid and dexamethasone also had inhibitory effects on MMP-2. Our results showed that cytokines, mitogens and inhibitors modulated FA fibroblast MMP-2 and MMP-9 expression, suggesting the clinical use of MMP inhibitors, particularly such potent and non-toxic ones as the NM and its component EGCG in the management of FA cancers.
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1 

Donahue SL and Campbell C: A DNA double strand break repair defect in Fanconi anemia fibroblasts. J Biol Chem. 277:46243–46247. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Donahue SL, Lundberg R, Saplis R and Campbell C: Deficient regulation of DNA double-strand break repair in Fanconi anemia fibroblasts. J Biol Chem. 278:29487–29495. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Epanchintsev A, Shyamsunder P, Verma RS and Lyakhovich A: IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism. Mol Carcinog. 54:1686–1699. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ibáñez A, Río P, Casado JA, Bueren JA, Fernández-Luna JL and Pipaón C: Elevated levels of IL-1β in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation. Biochem J. 422:161–170. 2009. View Article : Google Scholar : PubMed/NCBI

5 

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

6 

Stetler-Stevenson WG: The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis. Surg Oncol Clin N Am. 10:383–392. 2001.PubMed/NCBI

7 

Stetler-Stevenson WG: Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9:289–303. 1990. View Article : Google Scholar : PubMed/NCBI

8 

Sato T, Sakai T, Noguchi Y, Takita M, Hirakawa S and Ito A: Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol Oncol. 92:47–56. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Pyke C, Kristensen P, Ralfkiaer E, Grøndahl-Hansen J, Eriksen J, Blasi F and Danø K: Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol. 138:1059–1067. 1991.PubMed/NCBI

10 

Vincenti MP, White LA, Schroen DJ, Benbow U and Brinckerhoff CE: Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): Mechanisms that control enzyme activity, transcription and mRNA stability. Crit Rev Eukaryot Gene Expr. 6:391–411. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Ray JM and Stetler-Stevenson WG: The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis. Eur Respir J. 7:2062–2072. 1994.PubMed/NCBI

12 

Apodaca G, Rutka JT, Bouhana K, Berens ME, Giblin JR, Rosenblum ML, McKerrow JH and Banda MJ: Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res. 50:2322–2329. 1990.PubMed/NCBI

13 

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

14 

Roomi MW, Monterrey JC, Kalinovsky T, Rath M and Niedzwiecki A: Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines. Oncol Rep. 24:747–757. 2010.PubMed/NCBI

15 

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

16 

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

17 

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

18 

Mukhtar H and Ahmad N: Tea polyphenols: Prevention of cancer and optimizing health. Am J Clin Nutr. 71 Suppl 6:1698S–1704S. 2000.PubMed/NCBI

19 

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

20 

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

21 

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

22 

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

23 

Morini M, Cai T, Aluigi Mg, Noonan DM, Masiello L, De Flora S, D'Agostini 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

24 

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

25 

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

26 

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

27 

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

28 

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

29 

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

30 

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. 102:13604–13609. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Núñez M, Artín C and de Apodaca y Ruiz A Ortiz: 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). PubMed/NCBI

32 

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

33 

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

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Copy and paste a formatted citation
Spandidos Publications style
Roomi MW, Kalinovsky T, Rath M and Niedzwiecki A: Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts. Oncol Rep 37: 1842-1848, 2017.
APA
Roomi, M.W., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2017). Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts. Oncology Reports, 37, 1842-1848. https://doi.org/10.3892/or.2017.5368
MLA
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts". Oncology Reports 37.3 (2017): 1842-1848.
Chicago
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts". Oncology Reports 37, no. 3 (2017): 1842-1848. https://doi.org/10.3892/or.2017.5368
Copy and paste a formatted citation
x
Spandidos Publications style
Roomi MW, Kalinovsky T, Rath M and Niedzwiecki A: Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts. Oncol Rep 37: 1842-1848, 2017.
APA
Roomi, M.W., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2017). Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts. Oncology Reports, 37, 1842-1848. https://doi.org/10.3892/or.2017.5368
MLA
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts". Oncology Reports 37.3 (2017): 1842-1848.
Chicago
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Cytokines, inducers and inhibitors modulate MMP-2 and MMP‑9 secretion by human Fanconi anemia immortalized fibroblasts". Oncology Reports 37, no. 3 (2017): 1842-1848. https://doi.org/10.3892/or.2017.5368
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