Tumor invasion is the critical step that could lead to
metastasis in
retinoblastoma (RB), a common childhood
cancer.
Matrix metalloproteinases (
MMPs) degrade extracellular matrix, which is a crucial step involved in various stages of
tumor progression, including
tumor angiogenesis,
tumor growth, and also local invasion and subsequent distant
metastasis. We investigated the role of extracellular
MMP inducer (
EMMPRIN), MMP-2, MMP-9 and
tissue inhibitor of metalloproteinases (TIMPs):
TIMP-1,
TIMP-2 in RB and correlated clinicopathologically. Among 60
tumors,
EMMPRIN was expressed in 40 (64%), MMP-2 in 41 (66%), MMP-9 in 38 (61%),
TIMP-1 in 35 (56%), and
TIMP-2 in 33 (53%)
tumors.
EMMPRIN was positive (3+) in 13 (39%) out of 33
tumors with invasion and was positive (3+) in only 1 (3%) out of 29
tumors without invasion. MMP-2 (P<0.0001) and MMP-9 (P<0.0001) were significantly positive (3+) in 7 (21%) and 12 (36%) out of 33
tumors with invasion, whereas positive (3+) in 3 (10%) and faint (1+) in 10 (34%)
tumors, respectively, out of 29
tumors without invasion.
TIMP-1 (P<0.0001) and
TIMP-2 (P=0.04) were significantly positive (3+) in 7 (21%) and 10 (30%), respectively out of 33
tumors with invasion, whereas positive (3+) in only 1 (3%)
tumor each out of 29
tumors without invasion. Immunoblotting of
tumors confirmed the presence of
EMMPRIN,
MMPs, and TIMPs. In conclusion, both
MMPs and TIMPs may be involved RB invasion and
EMMPRIN could play a role in up-regulation of MMP-2 in invasive RB.