Matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) facilitate tumor in
vasion and metastasis via basement membrane degradation, In colorectal
cancer (CRC) specimens, MMP production is largely stromal in origin,
implicating monocytes (M phi s) and fibroblasts, We hypothesize that C
RC cells induce stromal cell MMP production, This study examines the d
ifferential effect of metastatic and non-metastatic CRC cells on M phi
MMP production, The human M phi line THP-1 was co-cultured with eithe
r a non-metastatic human CRC cell line (SW620-P) or a metastatic clone
(SW620-S5) established by serial cecal transplantation of SW620-P in
nude mice, Conditioned medium MMP activity and cellular MMP mRNA expre
ssion were assessed by gelatinase zymography and Northern blot analysi
s, respectively, Neither CRC line released MMP-2 or MMP-9, Isolated TH
P-1 M phi s produced basal levels of both MMP-2 and MMP-9, The level o
f MMP-9 activity was increased moderately by co-culture of M phi s wit
h the metastatic SW620-S5 clone, but decreased by the non-metastatic S
W620-P cells, MMP-2 activity was greatly augmented by co-culturing M p
hi s with SW620-S5 cells, but was not affected by SW620-P cells, The s
timulatory effect of SW620-S5 cells on MMP-2 secretion was confirmed b
y Western blot analysis, Both isolated and co-cultured M phi s express
ed MMP-2 mRNA while SW620-S5 cells under similar conditions did not, i
mplicating M phi s as the source of increased MMP-2 activity, Since th
e induction of MMP-2 activity was not associated with a parallel incre
ase in M phi MMP-2 mRNA, the modulation of M phi MMP-2 release appears
to be post-transcriptionally regulated. Metastatic CRC cells are dist
inct from non-metastatic cells in their ability to induce M phi MMP re
lease, This observation emphasizes the role of M phi-derived MMPs in f
acilitating CRC invasion and metastasis and suggests modulation of str
omal cell MMP production by CRC cells in a paracrine fashion.