Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors

被引:35
作者
Gokaslan, ZL
Chintala, SK
York, JE
Boyapati, V
Jasti, S
Sawaya, R
Fuller, G
Wildrick, DM
Nicolson, GL
Rao, JS
机构
[1] Univ Texas, MD Anderson Cancer Ctr, Dept Neurosurg, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Cancer Ctr, Dept Pathol, Houston, TX 77030 USA
[3] Inst Mol Med, Huntington Beach, CA 92649 USA
关键词
immunohistochemistry; MMPs; proteases; spinal metastases; TIMPs;
D O I
10.1023/A:1006580728338
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Matrix metalloproteinases (MMPs) have been implicated in the process of tumor invasion and metastasis formation, Thus, we determined the expression of MMPs in various primary and metastatic spinal tumors in order to assess the role of these enzymes in spinal invasion, MMP expression was examined by immunohistochemical localization, and quantitative evaluation of MMP protein content was determined by enzyme-linked immunosorbant assay (ELISA) and Western blotting. MMP enzyme activity was determined by gelatin zymography. Lung carcinomas and melanomas metastatic to the spine were shown to have higher levels of MMP-9 activity than those of breast, thyroid, renal metastases and primary spinal tumors. Immunohistochemical analysis revealed similar difference in expression of MMP-9 in tissue samples, When the tissue samples were subjected to gelatin zymography for examination of MMP-2 and MMP-9 activity and to ELISA and Western blotting for quantitative estimation of protein content, the most striking results were obtained for lung carcinomas and melanomas relative to the other tumors. Lung carcinomas and melanomas metastatic to the spine had considerably higher levels of MMP-9 activity than those of primary spinal tumor or breast, thyroid, acid renal carcinoma metastases, Within the metastatic tumor category, neoplasms that are known to be associated with the shortest overall survival rates and most aggressive behavior, such as lung carcinomas and melanomas, had the highest levels of MMP-2 and MMP-9 activity compared to those less aggressive metastatic tumors such as breast, renal cell, and thyroid carcinomas, Our results suggest that MMPs may contribute to the metastases to the spinal column, and overexpression of these enzymes may correlate with enhanced invasive properties of both primary and metastatic spinal tumors.
引用
收藏
页码:721 / 728
页数:8
相关论文
共 40 条
[1]   INHIBITION OF COLLAGENOLYTIC ACTIVITY AND METASTASIS OF TUMOR-CELLS BY A RECOMBINANT HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES [J].
ALVAREZ, OA ;
CARMICHAEL, DF ;
DECLERCK, YA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1990, 82 (07) :589-595
[2]   RAS ONCOGENE MEDIATED INDUCTION OF A 92KDA METALLOPROTEINASE - STRONG CORRELATION WITH THE MALIGNANT PHENOTYPE [J].
BALLIN, M ;
GOMEZ, DE ;
SINHA, CC ;
THORGEIRSSON, UP .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 154 (03) :832-838
[3]   SPINAL METASTASIS - CURRENT STATUS AND RECOMMENDED GUIDELINES FOR MANAGEMENT [J].
BLACK, P .
NEUROSURGERY, 1979, 5 (06) :726-746
[4]   THE TREATMENT OF CHORDOMAS [J].
CUMMINGS, BJ ;
ESSES, S ;
HARWOOD, AR .
CANCER TREATMENT REVIEWS, 1982, 9 (04) :299-311
[5]  
DECLERCK YA, 1992, CANCER RES, V52, P701
[6]   METASTATIC DISEASE OF THE SPINE [J].
HARRINGTON, KD .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1986, 68A (07) :1110-1115
[7]   PROGNOSTIC FACTORS IN GIANT-CELL TUMOR OF BONE - A MODIFIED HISTOLOGICAL GRADING SYSTEM USEFUL AS A GUIDE TO PROGNOSIS [J].
KOMIYA, S ;
INOUE, A ;
NAKASHIMA, M ;
UENO, A ;
FUJIKAWA, K ;
IKUTA, H .
ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY, 1986, 105 (02) :67-72
[8]  
KOSHIKAWA N, 1992, CANCER RES, V52, P5046
[9]  
KOSTUIK JP, 1991, ADULT SPINE PRINCIPL, P861
[10]  
Lang FF, 1996, NEUROSURG CLIN N AM, V7, P459