TY - JOUR
T1 - Up-regulation of SIBLING proteins and correlation with cognate MMP expression in oral cancer
AU - Ogbureke, Kalu U.E.
AU - Nikitakis, Nikolaos G.
AU - Warburton, Gary
AU - Ord, Robert A.
AU - Sauk, John J.
AU - Waller, Jennifer L.
AU - Fisher, Larry W.
N1 - Funding Information:
We thank Ms. Li Li (Craniofacial and Skeletal Disease Branch, NIDCR) for assistance with histologic tissue preparation and immunohistochemistry. We also thank Dr. Stephen Looney of the Department of Biostatistics, Medical College of Georgia, Augusta, Georgia, for assistance with statistical data presentation. This research was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH. A preliminary report of SIBLING localization in oral squamous cell carcinoma was presented at the 2005 IADR Annual Meeting in Baltimore, Maryland, USA
PY - 2007/10
Y1 - 2007/10
N2 - Various combinations of the SIBLING family of proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p < 0.0001), BSP and MMP-3 (p < 0.0001), and OPN and MMP-3 (p < 0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. While the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation.
AB - Various combinations of the SIBLING family of proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p < 0.0001), BSP and MMP-3 (p < 0.0001), and OPN and MMP-3 (p < 0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. While the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation.
KW - BSP
KW - DSPP
KW - Immunohistochemistry
KW - MMP-2
KW - MMP-3
KW - MMP-9
KW - OPN
KW - OSCC
KW - SIBLING proteins
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UR - http://www.scopus.com/inward/citedby.url?scp=34548480469&partnerID=8YFLogxK
U2 - 10.1016/j.oraloncology.2006.11.011
DO - 10.1016/j.oraloncology.2006.11.011
M3 - Article
C2 - 17306612
AN - SCOPUS:34548480469
SN - 1368-8375
VL - 43
SP - 920
EP - 932
JO - Oral Oncology
JF - Oral Oncology
IS - 9
ER -
