Strong clinical and experimental evidence demonstrates association of elevated levels of
matrix metalloproteinase MMP-9 with
cancer progression,
metastasis and shortened patient survival, as it plays a key role in
tumor cell invasion and
metastasis by digesting the basement membrane and ECM components. MMP-9 is secreted in both the monomeric and dimeric form. Although there is little research on MMP-9 dimers, some studies have shown the dimer to be associated with more aggressive
tumor progression. Our objective was to study the relative secretion patterns of MMP-9 monomer and dimer in a variety of
cancer cell lines and the effect of a nutrient mixture (NM) containing
lysine,
proline,
ascorbic acid and
green tea extract on MMP-9 secretion. The
cancer cell lines were grown in their respective media, supplemented with 10% FBS,
penicillin (100 U/ml) and
streptomycin (100 µg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with NM at 0,10, 50, 100, 500 and 1000 µg/ml. Parallel sets of cultures were treated with PMA (100 ng/ml) for induction of MMP-9. Cell MMP-9 secretion was assayed by
gelatinase zymography. MMP-9 dimer secretion patterns of
cancer cells fell into different categories. We observed no MMP-9 dimer in prostate DU-145 and PC-3, pancreatic MIA-Pa-Ca2, colon HCT-116, bladder T-24, head and neck FaDu,
glioblastoma A-172,
T-98 and LN-18 and
leukemia HL-60, Jurkat, and Raji cell lines.
MMP-dimer secretion only with PMA induction was seen in breast MCF-7 and MDA-MB-231, uterine SK-UT-1, lung A-549, tongue SC-25,
melanoma A2058,
osteosarcoma U-2OS,
rhabdomyosarcoma,
fibrosarcoma HT-1080,
chondrosarcoma SW-1350 and
liposarcoma SW-872. Cervical HeLa and DoTc 2 4510, renal 786-0 and HCC SK-Hep-1 cells exhibited MMP-9 dimer without PMA treatment and increased secretion with PMA treatment.
Sarcomas had the highest levels of MMP-9 monomer and dimer with and without PMA among these
cancer cell lines. Cervical, uterine and
male breast cancer cell lines showed the next highest levels of MMP-9, followed by
breast cancer cell lines.
Melanoma, renal, lung, head and neck and HCC showed lower levels and prostate,
glioblastoma, bladder and
leukemia cell lines the lowest. NM showed dose-dependent inhibition of MMP-9 monomer and dimer in all cell lines tested. In conclusion, high MMP-9 and dimer secretion levels correlated with the most aggressive
cancer cell lines. NM was effective in inhibiting MMP-9 and dimer secretion in all cell lines tested, suggesting its therapeutic potential as an antimetastatic agent.