In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by cytokines, inducers and inhibitors

Roomi,M. W.; Kalinovsky,T.; Monterrey,J.; Rath,M.; Niedzwiecki,A.

doi:10.3892/ijo.2013.2113

In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by cytokines, inducers and inhibitors

Authors:
- M. W. Roomi
- T. Kalinovsky
- J. Monterrey
- M. Rath
- A. Niedzwiecki
View Affiliations

Affiliations: Dr. Rath Research Institute, Santa Clara, CA 95050, USA
Published online on: September 30, 2013 https://doi.org/10.3892/ijo.2013.2113
Pages: 1787-1798
Copyright: © Roomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The highly aggressive adult sarcomas are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9, which play crucial roles in tumor invasion and metastasis by degradation of the extracellular membrane leading to cancer cell spread to distal organs. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 secretion in chondrosarcoma (SW-1353), fibrosarcoma (HT-1080), liposarcoma (SW-872) and synovial sarcoma (SW-982) cell lines. The selected compounds included natural cytokines and growth factors, as well as chemical compounds applied in therapy of sarcoma and natural compounds that have demonstrated anticancer therapeutic potential. MMP-2 and MMP-9 secretions were analyzed by gelatinase zymography following 24-h exposure to the tested agents and quantitated by densitometry. Fibrosarcoma, chondrosarcoma, liposarcoma and synovial sarcoma showed bands corresponding to MMP-2 and MMP-9 with dose-dependent enhancement of MMP-9 with phorbol 12-myristate 13-acetate (PMA) treatment. In chondrosarcoma cells, tumor necrosis factor (TNF)-α had a stimulatory effect on MMP-9 and insignificant effect on MMP-2 and interleukin (IL)-1β stimulated MMP-9 and MMP-2. In fibrosarcoma and liposarcoma cells, TNF-α had a profound stimulatory effect on MMP-9, but no effect on MMP-2 and in synovial sarcoma an inhibitory effect on MMP-2 and no effect on MMP-9. IL-1β had a slight inhibitory effect on fibrosarcoma, liposarcoma and synovial sarcoma MMP-2 and MMP-9 except for MMP-9 in synovial sarcoma which showed slight stimulation. Lipopolysaccharide (LPS) stimulated expression of MMP-2 in fibrosarcoma and chondrosarcoma while inhibited it in liposarcoma. Doxycycline, epigallocatechin gallate and the nutrient mixture inhibited MMP-2 and MMP-9 in all cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 and -9 in chondrosarcoma and fibrosarcoma cells. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in adult sarcoma cell lines, suggesting these agents may be effective strategies to treat these cancers.

View Figures

View References

1.	American Cancer Society: Adult soft tissue cancer. What are the key statistics about soft tissue sarcomas? http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-key-statistics. Last revised October 2, 2012. Accessed January 21, 2013.
2.	American Cancer Society: Bone cancer. What are the key statistics about bone cancer? http://www.cancer.org/cancer/bonecancer/detailedguide/bone-cancer-key-statistics. Last revised November 29, 2012. Accessed January 21, 2013.
3.	Papagelopoulos PJ, Galanis E, Frassica FJ, Sim FH, Larson DR and Wold LE: Primary fibrosarcoma of bone. Outcome after primary surgical treatment. Clin Orthop Relat Res. 373:88–103. 2000.PubMed/NCBI
4.	Benassi MS, Gamberi G, Magagnoli G, Molendini L, Ragazzini P, Merli M, Chiesa F, Balladelli A, Manfrini M, Bertoni F, Mercri M and Picci P: Metalloproteinase expression and prognosis in soft tissue sarcomas. Ann Oncol. 12:75–80. 2001. View Article : Google Scholar : PubMed/NCBI
5.	Nelson AR, Fingleton B, Rothenberg ML and Matrisian LM: Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 18:1135–1149. 2000.PubMed/NCBI
6.	Liotta LA, Tryggvason K, Garbisa A, 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
7.	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
8.	Stetler-Stevenson WG: Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9:289–303. 1990. View Article : Google Scholar : PubMed/NCBI
9.	Sato T, Sakai T, Noguchi Y, Takta 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
10.	Pyke C, Kristensen P, Ralfkiaer E, Gröndahl-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
11.	Harvey P, Clark IM, Jourand MC, Warn RM and Edwards DR: Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases. Br J Cancer. 83:1147–1153. 2000. View Article : Google Scholar : PubMed/NCBI
12.	Liu Z, Ivanoff A and Klominek J: Expression and activity of matrix metalloproteases in human malignant mesothelioma cell lines. Int J Cancer. 91:638–643. 2001. View Article : Google Scholar : PubMed/NCBI
13.	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
14.	Rutkowski P, Kaminska J, Kowalska M, Ruka W and Steffen J: Cytokine and cytokine receptor serum levels in soft tissue sarcoma patients: correlations with clinico-pathological features and prognosis. Int J Cancer. 100:463–471. 2002. View Article : Google Scholar : PubMed/NCBI
15.	Ray JM and Stetler-Stevenson WG: The role of matrix metalloproteinase and their inhibitors in tumour invasion, metastasis and angiogenesis. Eur Respir J. 7:2062–2072. 1994.PubMed/NCBI
16.	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
17.	Linder C, Linder S, Munck-Wickland E and Strander H: Independent expression of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with carcinoma and sarcoma. Anticancer Res. 18:2063–2068. 1998.PubMed/NCBI
18.	Graeven U, Andre N, Achilles E, Zornig C and Schmeigel W: Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in patients with soft-tissue sarcoma. J Cancer Res Clin Oncol. 125:577–581. 1999. View Article : Google Scholar : PubMed/NCBI
19.	Rutkowski P, Kaminska J, Kowalska M, Ruka W and Steffen J: Cytokine and cytokine receptor serum levels in adult bone sarcoma patients: correlations with local tumor extent and prognosis. J Surg Oncol. 84:151–159. 2003. View Article : Google Scholar : PubMed/NCBI
20.	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. 29:529–543. 2010. View Article : Google Scholar : PubMed/NCBI
21.	Roomi MW, Monterrey JC, Kalinovsky T, Niedzwiecki A and Rath M: Inhibition of invasion and MMPs by a nutrient mixture in human cancer cell lines: a correlation study. Exp Oncol. 32:243–248. 2010.PubMed/NCBI
22.	Roomi MW, Ivanov V, Kalinovsky T, Rath M and Niedzwiecki A: In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline, arginine and green tea extract on human fibrosarcoma cells HT-1080. Med Oncol. 23:105–112. 2006. View Article : Google Scholar : PubMed/NCBI
23.	Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A and Rath M: In vitro and in vivo anti-tumor effect of a nutrient mixture containing ascorbic acid, lysine, proline and green tea extract on human synovial sarcoma cancer cells. JANA . 9:22006.
24.	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
25.	Rath M and Pauling L: Plasmin-induced proteolysis and the role of apoprotein(a), lysine and synthetic analogs. Orthomolecular Med. 7:17–23. 1992.
26.	Sun Z, Chen YH, Wang P, Zhang J, Gurewich V, Zhang P and Liu JN: The blockage of high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochem Biophys Acta. 1596:182–192. 2002.PubMed/NCBI
27.	Valcic S, Timmermann BN, Alberts DS, Wachter GA, Krutzsch M, Wymer J and Guillen 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
28.	Mukhtar H and Ahmed N: Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr. 71(Suppl 6): 1698–1704. 2000.PubMed/NCBI
29.	Yang GY, Liao J, Kim K, Yurtow 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
30.	Taniguchi S, Fujiki H, Kobayashi H, Go H, Miyado K, Sadano H and Shimikawa 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.
31.	Hara Y: Green Tea: Health Benefits and Applications . Marcel Dekker; New York, Basel: 2001, View Article : Google Scholar
32.	Kawakami S, Kageyama Y, Fujii Y, Kihara K and Oshima H: Inhibitory effects of N-acetyl cysteine on invasion and MMP 9 production of T24 human bladder cancer cells. Anticancer Res. 21:213–219. 2001.PubMed/NCBI
33.	Morini M, Cai T, Aluigi MG, Noonan DM, Masiello L, De Floro S, D'Agostinin F, Albini A and Fassima G: The role of the thiol N-acetyl cysteine in the prevention of tumor invasion and angiogenesis. Int J Biol Markers. 14:268–271. 1999.PubMed/NCBI
34.	Yoon SO, Kim MM and Chung AS: Inhibitory effects of selenite on invasion of HT 1080 tumor cells. J Biol Chem. 276:20085–20092. 2001. View Article : Google Scholar : PubMed/NCBI
35.	Naidu KA, Karl RC 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
36.	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
37.	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
38.	Koh WS, Lee SJ, Lee H, Park C, Park MH, Kim WS, Yoon SS, Park K, Hong SI, Chung MH and Park CH: Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. Anticancer Res. 8:2487–2493. 1998.PubMed/NCBI
39.	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
40.	Nunez C, Ortiz de Apodaca Y and Ruiz A: Ascorbic acid in the plasma and blood cells of women with breast cancer. The effect of consumption of food with an elevated content of this vitamin. Nutr Hosp. 10:368–372. 1995.(In Spanish).
41.	Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D and Bruckner HW: Ascorbic acid (vitamin C) improves the anti neoplastic 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
42.	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