Affiliations: Bioinformatics Program, University of Michigan, Ann
Arbor, MI 48109, USA | Departments of Pediatrics and Communicable Diseases,
University of Michigan, Ann Arbor, MI 48109, USA
Note: [] Corresponding author: Chad Creighton, Bioinformatics Program,
University of Michigan, Ann Arbor, MI 48109, USA. Tel.: +1 734 763 0917; Fax:
+1 734 615 4637; E-mail: [email protected]
Abstract: Matrix metalloproteinases (MMPs) are endopeptidases considered to be
important regulators of the microenvironment of cancer. While MMPs are
traditionally associated with the extracellular matrix (ECM), here we provide
new evidence from an analysis of gene expression profiles from human tumor
tissue that MMP-9 (gelatinase B) is associated with elements of the immune
system in a way analogous to the association of other MMPs, such as MMP-2
(gelatinase A), with components of the ECM. An analysis of three independent
microarray datasets of lung adenocarcinomas from previous studies [Nat. Med. 8,
816–824 (2002); Proc. Natl. Acad. Sci. USA 98, 13790–13795 (2001); Proc. Natl.
Acad. Sci. USA, 98, 13784–13789 (2001)] showed that, in each dataset, out of the
set of genes with significant correlations in mRNA expression to the expression
of MMP9 (P < 0.005), a highly disproportionate number were found to be
annotated in the Locuslink database as having a role in the anti-pathogen
response. By comparison, out of the set of genes significantly correlated with
the expression of MMP2, a highly disproportionate number were known components
of the ECM. The same patterns observed in the lung data for both MMP2 and MMP9
were found as well in an additional published dataset of colon and ovarian
adenocarcinomas [Am. J. Pathol. 159, 1231–1238 (2001)]. The results of this
study suggest a greater functional role for MMP-9 in the immune response to
cancer than what may previously have been thought.
Keywords: matrix metalloproteinases, microarrays, MMP9, data mining, immune response
