Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine.
Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.
Shariftabrizi
Ahmad
A
Department of Pathobiology, Tehran University of Medical Sciences, Iran.
Nifli
Artemissia-Phoebe
AP
Ansari
Mohammad
M
Saadat
Farshid
F
Ebrahimkhani
Mohammad Reza
MR
Alizadeh
Nastaran
N
Nasseh
Azadeh
A
Alexaki
Vassilia-Ismini
VI
Dehpour
Ahmad Reza
AR
Castanas
Elias
E
Khorramizadeh
Mohammad Reza
MR
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004174:Diprenorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D011957:Receptors, Opioid; D004174:Diprenorphine; D009569:Nitric Oxide; D009020:Morphine; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2; D019331:NG-Nitroarginine Methyl Ester