PMID- 28440509
DCOM- 20180301
LR  - 20180301
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 37
IP  - 6
DP  - 2017 Jun
TI  - Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in
      human melanoma A-2058 cells.
PG  - 3681-3687
LID - 10.3892/or.2017.5597 [doi]
AB  - 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-alpha and 
      IL-1beta at 0.1, 1, 10 and 25 ng/ml; LPS at 10, 25, 50 and 100 microg/ml;
      epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10, 25, 50 and 100
      microM 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 microg/ml; actinomycin D and cyclohexamide at 2 and 4 microM; retinoic acid
      and dexamethasone at 50 microM. 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-alpha 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-1beta 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 microg/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.
FAU - Roomi, M Waheed
AU  - Roomi MW
AD  - Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
FAU - Kalinovsky, Tatiana
AU  - Kalinovsky T
AD  - Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
FAU - Niedzwiecki, Aleksandra
AU  - Niedzwiecki A
AD  - Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
FAU - Rath, Matthias
AU  - Rath M
AD  - Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
LA  - eng
PT  - Journal Article
DEP - 20170424
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC (Matrix Metalloproteinase 2)
RN  - EC (MMP9 protein, human)
RN  - EC (Matrix Metalloproteinase 9)
RN  - N12000U13O (Doxycycline)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Catechin/administration & dosage/analogs & derivatives
MH  - Cell Line, Tumor
MH  - Cytokines/administration & dosage/metabolism
MH  - Doxycycline/administration & dosage
MH  - Humans
MH  - Interleukin-1beta/administration & dosage/metabolism
MH  - Matrix Metalloproteinase 2/biosynthesis/*genetics
MH  - Matrix Metalloproteinase 9/biosynthesis/*genetics
MH  - Matrix Metalloproteinase Inhibitors/*administration & dosage
MH  - Melanoma/*drug therapy/genetics/pathology
MH  - Tetradecanoylphorbol Acetate/administration & dosage
MH  - Tumor Necrosis Factor-alpha/administration & dosage/metabolism
EDAT- 2017/04/26 06:00
MHDA- 2018/03/02 06:00
CRDT- 2017/04/26 06:00
PHST- 2017/01/12 00:00 [received]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/04/26 06:00 [pubmed]
PHST- 2018/03/02 06:00 [medline]
PHST- 2017/04/26 06:00 [entrez]
AID - 10.3892/or.2017.5597 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Jun;37(6):3681-3687. doi: 10.3892/or.2017.5597. Epub 2017 Apr 24.