title: Inhibition of invasion and MMPs by a nutrient mixture in human cancer cell lines: a correlation study.
abstract: Matrix metalloproteinase (MMP)-2 and -9 secretion is elevated in various human cancers and their elevated expression has been associated with poor prognosis due to associated increased cancer cell invasion and metastasis.
  
  
  OBJECTIVE
  To examine the correlation between in vitro MMP-2 and MMP-9 secretion and Matrigel invasion in 42 different human cancer cell lines (selected on the basis of organ malignancies) treated with a nutrient mixture (NM).
  
  
  METHODS
  The cells were cultured in their recommended media supplemented with 10% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were treated with NM dissolved in media at 0, 10, 50, 100, 500 and 1000 μg/mL in triplicate. Parallel sets of cultures were also treated with phorbol 12-myristate 13-acetate (PMA) 100 ng/mL for induction of enzymes. After 24 h the media were collected and MMP-2 and MMP-9 levels were assayed by gelatinase zymography. Invasion studies were conducted using Matrigel in 24-well plates.
  
  
  RESULTS
  Correlation of pooled data from different cancer cell line groups demonstrated dose-dependent inhibition of MMP-2 and -9 and Matrigel invasion with NM treatment and significant negative correlation between MMP-2 and MMP-9 levels and Matrigel invasion. Pooled data of cell lines expressing only MMP-2 and resistance to PMA induction of MMP-9 showed significant negative correlation (r = -0.77, p = 0.003) between MMP-2 secretion and inhibition of invasion through Matrigel. Cell lines expressing only MMP-9, showed significant negative correlation (r = -0.726, p = 0.003) between MMP-9 secretion and Matrigel invasion. Pooled data of cell lines expressing MMP-2 and MMP-9 demonstrated significant negative correlation (r = -0.821, p < 0.0001) between MMP-9 secretion and inhibition of invasion through Matrigel. Pooled data of cancer cell lines expressing no basal MMP- 9 secretion demonstrated significant negative correlation (r = -0.686, p < 0.0001) between PMA-induced MMP-9 secretion and inhibition of invasion through Matrigel.
  
  
  CONCLUSIONS
  In conclusion, regardless of MMP-2 and MMP-9 patterns of expression, MMP modulation by NM was found to be significantly correlated with NM modulation of Matrigel invasion of these cell lines.
authors.affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Roomi
authors.forename: J C
authors.initials: JC
authors.lastname: Monterrey
authors.forename: T
authors.initials: T
authors.lastname: Kalinovsky
authors.forename: M
authors.initials: M
authors.lastname: Rath
authors.forename: A
authors.initials: A
authors.lastname: Niedzwiecki
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9