Expression of matrix metalloproteinases and their inhibitors in retinoblastoma.
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.
Adithi
Mohan
M
Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India.
Nalini
Venkatesan
V
Kandalam
Mallikarjuna
M
Krishnakumar
Subramanian
S
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005134:Eye Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012016:Reference Values; D012160:Retina / Q000201:enzymology; D012175:Retinoblastoma / Q000201:enzymology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases