EMMPRIN和MMP-2的表达与喉癌侵袭、转移关系的研究
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摘要
目的 喉癌是头颈部的常见恶性肿瘤，喉癌的侵袭、转移是致死的主要原因，而肿瘤的侵袭与由细胞外基质金属蛋白酶诱导因子(extracellular matrix metalloproteinase inducer,EMMPRIN)诱导肿瘤周围成纤维细胞合成、分泌的基质金属蛋白酶(matrix metalloproteinases,MMPs)介导的细胞外基质的降解有着密切的关系。本研究的目的在于了解EMMPRIN和MMP-2在喉癌的表达情况，探讨两者之间以及与喉癌的侵袭和转移的关系。
方法 用免疫组织化学S-P法对47例喉癌和22例正常喉组织中的EMMPRIN和MMP-2的表达情况进行检测，分析EMMPRIN和MMP-2的表达与喉癌的临床病理特征之间的关系，以及两者的相关性。
结果 EMMPRIN和MMP-2在喉癌的阳性表达率(分别为87.2％和91.5％)明显高于正常喉组织(分别为9.1％和18.2％)；EMMPRIN和MMP-2的强阳性表达与喉癌的病理分级、临床分期和颈淋巴结转移情况有关；EMMPRIN和MMP-2的表达一致率为85.1％，Kappa值为0.803，两者的表达具有明显的相关性。
结论 作为降解细胞外基质和基底膜的胶原酶，MMP-2和其上
南京医科大学硕一}学位论文
游的诱导因子EMMP咫N在喉癌组织有阳性表达，表达的
强度与喉癌的病理分级、临床分期和颈淋巴结转移情况有
关，EMMP租N与MMP一2的表达可作为诊断喉癌，了解喉
癌侵袭性的一个生物学标志。
Objective Laryngeal carcinoma is the common malignant tumor in head and neck, and the tumor cell invasion of laryngeal carcinoma is responsible for both local destruction and metastasis. Invasion is largely mediated by matrix metalloproteinases that is thought to be induced by extracellular matrix metalloproteinase inducer (EMMPRIN) in surrounding fibroblasts. The aim of this research is to investigate the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-2 in human laryngeal carcinoma, and to learn the relationship between the expressions and with the clinicopathological features. Methods The expressions of EMMPRIN and MMP-2 were detected by the method of immunohistochemical S-P in 47 specimens of laryngeal carcinoma and 22 specimens of normal laryngeal tissues. The relationship between the expressions and with the clinicopathological features was analysed. Results Positive expression rates of EMMPRIN and MMP-2 in laryngeal carcinoma were 87.2% and 91.5% re
spectively, higher than 9.1% and 18.2% in normal laryngeal tissues. In laryngeal carcinoma, the intensive expression rates of EMMPRIN and MMP-2 had a positive
relationship with histopathological grade, clinical phase and the situation of cervical lymph node matastasis. The co-expression rate of EMMPRIN and MMP-2 was 85.1%. Significant correlation was found between the expression of EMMPRIN and that of MMP-2 in laryngeal carcinoma. Conclusion As the major enzyme to degrade native collagen type IV, a main component of extracellular matrix and basement membrane, MMP-2 and its inducer, EMMPRIN express in laryngeal carcinoma. The expressions of EMMPRIN and MMP-2 have relevance to histopathological grade, clinical stage and cervical lymph node matastasis of laryngeal carcinoma. Increased expression of MMP-2 might be induced by EMMPRIN expressed in laryngeal tumor cells. The expression of MMP-2 and EMMPRIN may be a biological mark to diagnose and learn the invasive ability of laryngeal carcinoma.
方法 用免疫组织化学S-P法对47例喉癌和22例正常喉组织中的EMMPRIN和MMP-2的表达情况进行检测，分析EMMPRIN和MMP-2的表达与喉癌的临床病理特征之间的关系，以及两者的相关性。
结果 EMMPRIN和MMP-2在喉癌的阳性表达率(分别为87.2％和91.5％)明显高于正常喉组织(分别为9.1％和18.2％)；EMMPRIN和MMP-2的强阳性表达与喉癌的病理分级、临床分期和颈淋巴结转移情况有关；EMMPRIN和MMP-2的表达一致率为85.1％，Kappa值为0.803，两者的表达具有明显的相关性。
结论 作为降解细胞外基质和基底膜的胶原酶，MMP-2和其上
南京医科大学硕一}学位论文
游的诱导因子EMMP咫N在喉癌组织有阳性表达，表达的
强度与喉癌的病理分级、临床分期和颈淋巴结转移情况有
关，EMMP租N与MMP一2的表达可作为诊断喉癌，了解喉
癌侵袭性的一个生物学标志。
Objective Laryngeal carcinoma is the common malignant tumor in head and neck, and the tumor cell invasion of laryngeal carcinoma is responsible for both local destruction and metastasis. Invasion is largely mediated by matrix metalloproteinases that is thought to be induced by extracellular matrix metalloproteinase inducer (EMMPRIN) in surrounding fibroblasts. The aim of this research is to investigate the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-2 in human laryngeal carcinoma, and to learn the relationship between the expressions and with the clinicopathological features. Methods The expressions of EMMPRIN and MMP-2 were detected by the method of immunohistochemical S-P in 47 specimens of laryngeal carcinoma and 22 specimens of normal laryngeal tissues. The relationship between the expressions and with the clinicopathological features was analysed. Results Positive expression rates of EMMPRIN and MMP-2 in laryngeal carcinoma were 87.2% and 91.5% re
spectively, higher than 9.1% and 18.2% in normal laryngeal tissues. In laryngeal carcinoma, the intensive expression rates of EMMPRIN and MMP-2 had a positive
relationship with histopathological grade, clinical phase and the situation of cervical lymph node matastasis. The co-expression rate of EMMPRIN and MMP-2 was 85.1%. Significant correlation was found between the expression of EMMPRIN and that of MMP-2 in laryngeal carcinoma. Conclusion As the major enzyme to degrade native collagen type IV, a main component of extracellular matrix and basement membrane, MMP-2 and its inducer, EMMPRIN express in laryngeal carcinoma. The expressions of EMMPRIN and MMP-2 have relevance to histopathological grade, clinical stage and cervical lymph node matastasis of laryngeal carcinoma. Increased expression of MMP-2 might be induced by EMMPRIN expressed in laryngeal tumor cells. The expression of MMP-2 and EMMPRIN may be a biological mark to diagnose and learn the invasive ability of laryngeal carcinoma.
引文
1．杨成章．喉部恶性肿瘤．见：黄选兆，汪吉宝主编．实用耳鼻咽喉科学．北京：人民卫生出版社，1998：502．
2. Liotta L A, Stetler-Stevenson W G. Tumor invasion and matastasis:an imbalance of positive and negitive regulation[J].Cancer Res, 1991, 51(18):5054-5059.
3. Bogusiewicz M, Stryjecka-Zimmer M, Szymanski M, et al. Activity of matrix metalloproteinases-2 and -9 in advanced laryngeal cancer. Otolaryngol Head Neck Surg, 2003,128(1):132-136.
4. Kawata R, Shimada T, Maruyama S, et al. Enhanced production of matrix metalloproteinase-2 in human head and neck carcinomas is correlated with lymph node metastasis. Acta Otolaryngol, 2002,122(1):101-106
5．杜波，王苹，郭晓峰等．血清基质蛋白酶-2的表达与喉癌的转移．耳鼻咽喉-头颈外科，2001，8(4)：229-231．
6．李正贤，刘庚勋，李学佩．MMP-9和WTIMP-2在喉癌中的表达及其临床意义．耳鼻咽喉-头颈外科，2002，9(5)：306-309．
7. Rosenthal EL, Shreenivas S, Peters GE, et al. Expression of extracellular matrix metalloproteinase inducer in laryngeal squamous cell carcinoma. Laryngoscope. 2003,113(8):1406-1410
8. Sameshima T, Nabeshima K, Toole BP, et al. Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. Int J Cancer, 2000,88(1):21-27.
9. Bordador LC, Li X, Toole B, et aL. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer. 2000;85(3):347-352.
10. Caudroy S, Polette M, Tournier JM, et al. Expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase-2 in bronchopulmonary and breast lesions. J Histochem Cytochem. 1999,47(12):1575-1580.
11．王贤辉，陈志南，郭晓楠．CD147分子与MMPs在肝癌细胞系中表达的相关性．第四军医大学学报，2001，22(3)：217-219．
12．杜宽航，郭善禹，卜文．细胞外基质金属蛋白酶诱导因子在大肠癌中的表达．上海第二医科大学学报，2002，22(2)：115-117．
13. Davidson B, Goldberg I, Berner A, et al. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis. 2003,20(2):161-9.
14．陈翔，金藏拓郎[日]，张桂英等．皮肤鳞状细胞癌转移灶中基质金属蛋白酶的表达．湖南医科大学学报，2001，26(4)：297-300．
15．贺书云，辛晓燕，王健．基质金属蛋白酶2及CD147在卵巢上皮性肿瘤中的表达．第四军医大学学报，2001，22(5)：435-438．
16．陈翔，金藏拓郎，张桂英等．皮肤鳞状细胞癌中Basigin／CD147表达与肿瘤进展的相关性．中华皮肤科杂志，2002，35(4)：272-275．
17. Dalberg K, Eriksson E, Enberg U, et al. Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer. World J Surg, 2000,24(3):334-340.
18. Thorns C, Feller AC, Merz H. EMMPRIN (CD 174) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases. Anticancer Res, 2002,22(4):1983-1986.
19. Major TC, Liang L, Lu X, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced uponmonocyte differentiation and is expressed in human atheroma. Arterioscler Thromb Vasc Biol, 2002, 22(7):1200-1207.
20. Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer, 2002, 99(4):520-528.
21．吴学愚主编．耳鼻咽喉科全书·喉科学．第2版．上海：上海科学技术出版社，2000：321～322．
22. Shiraga M, Yano S, Yamamoto A, et al. Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines. Cancer Res, 2002, 62(20): 5967-5973.
23. Willam R. Matrix metalloprotainsese and carcinogenesis. Human pathology, 1999,30(4):363-367.
24. Maatta M, Soini Y, Liakka A, et al. Differential expression of matrix metalloproteinase MMP-2, MMP-9, and membrane type 1-MMP in human hepatocellular and pancreatic adenocarcinomas: implication of tumon progression and clinical pregnoss[J]. Clin Cancer Res, 2000, 6(7): 2726-2731
25. Hanemaaijer R, Verheijen JH, Maguire TM, et al. Incereased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors, Int J Cancer, 2000,86(2):204-207.
26. Ohtani H, Tabata N, Nagura, et al. Immunoelectron microscopic localization of gelatinase A in human gastyointestinal and skin carcinomas:difference between cancer cells and fibroblasts. Japan jJ Cancer Res, 1995,86(3):304-309.
27. Monig SP, Baldus SE, Hennecken JK, et al. Expression of MMP-2 associated with progression and lymph node metastasis of gastric carcinoma. Histopathology, 2001,39(4):597.
28. Ding Y, Shimada Y, Gorrin-Rivas M J, et al. Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma. Oncology, 2002,63(4): 378-384.
29．周彩云，姚济芬，陈晓瑞，等．基质金属蛋白酶MMP-2、MMP-9及其抑制剂TIMP-1、2在子宫颈鳞癌中表达的研究．癌症，2002，2(7)：735-737．
30. Kawata R, Shimada T, Maruyama S, et al. Enhanced production of matrix metalloproteinase-2 in human head and neck carcinomas is correlated with lymph node metastasis. Acta-Otolaryngol, 2002,122(1): 101-106.
31. Miyajima Y, Nakano R,Morimatsu M. Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization. Ann Otol Rhinol larygol, 1995,104(6):678-684.
32. Hoessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J, 1991,5(8):2145-2154.
33. Franchi A, Santucci M, Masini E, et al. Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck. Cancer, 2002, 95(9): 1902-1910.
34. Kataoka H, Tanaka H, Nagaike K, et al. Role of cancer cell-stroma interaction in invasive growth of cancer cells. Hum Cell. 2003,16(1):1-14.
35. Charous SJ, Stricklin GP, Nanney LB, et al. Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol, 1997,106(4): 271-278.
36. Krecicki T, Zalesska-Krecicka M, Jelen, et al. Expression of type Ⅳ collagen and matrix metalloproteinase-2 (type Ⅳ collagenase) in relation to nodal status in laryngeal cancer. Clin-Otolaryngol, 2001, 26(6): 469-472.
37. Ellis S, Nabeshima K, Biswas C. Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res, 1989,49(5):3385-3391.
38. Zucker S, Hymowitz M, Rollo EE, et al. Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol, 2001,158(6):1921-1928.
39. Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res, 2001,61(5):2276-2281.
40. Biswas C, Zhang Y, DeCastro R, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995,55(2):434-439.
41. Guo H, Majmudar G, Jensen T C , et al. Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of matrix metalloproteinases. Gene, 1998, 220(1-2): 99-108
42．金伯泉．白细胞分化抗原[M]．金伯泉主编，细胞和分子免疫学，第二版．北京：科学出版社，2001：4-7
43. Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res, 2000,60(4):888-891.
44. Lim M, Martinez T, Jablons D, et al. Tumor-derived EMMPRIN (extracellular matrix metalloproteinase inducer) stimulates collagenase transcription through MAPK p38. FEBS-Lett, 1998, 441(1): 88-92
45. Taylor PM, Woodfield RJ, Hodgkin MN, et al. Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP-2 release through a phospholipase A(2) and 5-1ipoxygenase catalyzed pathway. Oncogene, 2002,21(37):5765-5772.
46. Caudroy S, Polette M, Nawrocki-Raby B, et al. EMMPRIN-mediated MMP regulation in tumor and endothelial cells. Clin Exp Metastasis, 2002,19(8):697-702.
47. Li R, Huang L, Guo H, Toole BP. Basigin (murine EMMPRIN) stimulates matrix metalloproteinase production by fibroblasts. J Cell Physiol, 2001,186(3):3711-3719.
48. van den Oord JJ, Paemen L, Opdenakker G, et al. Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. Am J Pathol, 1997,151(3):665-670.
49. Polette M, Gilles C, Marchand V, et al. Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers. J Histochem Cytochem, 1997,45(5):703-709.
50. Guo H, Zucker S, Gordon MK, et al. Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells. J Biol Chem, 1997,272(1):24-27.
51. Matter .Tumor angiogenesis as a therapeutic target. DDT, 2001, 6(19):1005-1024.
52. Liang L, Major T, Bocan T. Characterization of the promoter of human extracellular matrix metalloproteinase inducer (EMMPRIN). Gene, 2002,282(1-2):75-86.
53．商澎，骞爱荣，胡佩珍，等．HAb18G／CD147拮抗肽对体内血管生成的影响．中国药理学学报，2003，19(3)：355-357．
54．杨红，郑维国，辛晓燕，等．CD147反义核酸对卵巢癌细胞生物学行为的影响．第四军医大学学报，2002，23(18)：1657-1659．
2. Liotta L A, Stetler-Stevenson W G. Tumor invasion and matastasis:an imbalance of positive and negitive regulation[J].Cancer Res, 1991, 51(18):5054-5059.
3. Bogusiewicz M, Stryjecka-Zimmer M, Szymanski M, et al. Activity of matrix metalloproteinases-2 and -9 in advanced laryngeal cancer. Otolaryngol Head Neck Surg, 2003,128(1):132-136.
4. Kawata R, Shimada T, Maruyama S, et al. Enhanced production of matrix metalloproteinase-2 in human head and neck carcinomas is correlated with lymph node metastasis. Acta Otolaryngol, 2002,122(1):101-106
5．杜波，王苹，郭晓峰等．血清基质蛋白酶-2的表达与喉癌的转移．耳鼻咽喉-头颈外科，2001，8(4)：229-231．
6．李正贤，刘庚勋，李学佩．MMP-9和WTIMP-2在喉癌中的表达及其临床意义．耳鼻咽喉-头颈外科，2002，9(5)：306-309．
7. Rosenthal EL, Shreenivas S, Peters GE, et al. Expression of extracellular matrix metalloproteinase inducer in laryngeal squamous cell carcinoma. Laryngoscope. 2003,113(8):1406-1410
8. Sameshima T, Nabeshima K, Toole BP, et al. Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. Int J Cancer, 2000,88(1):21-27.
9. Bordador LC, Li X, Toole B, et aL. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer. 2000;85(3):347-352.
10. Caudroy S, Polette M, Tournier JM, et al. Expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase-2 in bronchopulmonary and breast lesions. J Histochem Cytochem. 1999,47(12):1575-1580.
11．王贤辉，陈志南，郭晓楠．CD147分子与MMPs在肝癌细胞系中表达的相关性．第四军医大学学报，2001，22(3)：217-219．
12．杜宽航，郭善禹，卜文．细胞外基质金属蛋白酶诱导因子在大肠癌中的表达．上海第二医科大学学报，2002，22(2)：115-117．
13. Davidson B, Goldberg I, Berner A, et al. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis. 2003,20(2):161-9.
14．陈翔，金藏拓郎[日]，张桂英等．皮肤鳞状细胞癌转移灶中基质金属蛋白酶的表达．湖南医科大学学报，2001，26(4)：297-300．
15．贺书云，辛晓燕，王健．基质金属蛋白酶2及CD147在卵巢上皮性肿瘤中的表达．第四军医大学学报，2001，22(5)：435-438．
16．陈翔，金藏拓郎，张桂英等．皮肤鳞状细胞癌中Basigin／CD147表达与肿瘤进展的相关性．中华皮肤科杂志，2002，35(4)：272-275．
17. Dalberg K, Eriksson E, Enberg U, et al. Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer. World J Surg, 2000,24(3):334-340.
18. Thorns C, Feller AC, Merz H. EMMPRIN (CD 174) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases. Anticancer Res, 2002,22(4):1983-1986.
19. Major TC, Liang L, Lu X, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced uponmonocyte differentiation and is expressed in human atheroma. Arterioscler Thromb Vasc Biol, 2002, 22(7):1200-1207.
20. Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer, 2002, 99(4):520-528.
21．吴学愚主编．耳鼻咽喉科全书·喉科学．第2版．上海：上海科学技术出版社，2000：321～322．
22. Shiraga M, Yano S, Yamamoto A, et al. Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines. Cancer Res, 2002, 62(20): 5967-5973.
23. Willam R. Matrix metalloprotainsese and carcinogenesis. Human pathology, 1999,30(4):363-367.
24. Maatta M, Soini Y, Liakka A, et al. Differential expression of matrix metalloproteinase MMP-2, MMP-9, and membrane type 1-MMP in human hepatocellular and pancreatic adenocarcinomas: implication of tumon progression and clinical pregnoss[J]. Clin Cancer Res, 2000, 6(7): 2726-2731
25. Hanemaaijer R, Verheijen JH, Maguire TM, et al. Incereased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors, Int J Cancer, 2000,86(2):204-207.
26. Ohtani H, Tabata N, Nagura, et al. Immunoelectron microscopic localization of gelatinase A in human gastyointestinal and skin carcinomas:difference between cancer cells and fibroblasts. Japan jJ Cancer Res, 1995,86(3):304-309.
27. Monig SP, Baldus SE, Hennecken JK, et al. Expression of MMP-2 associated with progression and lymph node metastasis of gastric carcinoma. Histopathology, 2001,39(4):597.
28. Ding Y, Shimada Y, Gorrin-Rivas M J, et al. Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma. Oncology, 2002,63(4): 378-384.
29．周彩云，姚济芬，陈晓瑞，等．基质金属蛋白酶MMP-2、MMP-9及其抑制剂TIMP-1、2在子宫颈鳞癌中表达的研究．癌症，2002，2(7)：735-737．
30. Kawata R, Shimada T, Maruyama S, et al. Enhanced production of matrix metalloproteinase-2 in human head and neck carcinomas is correlated with lymph node metastasis. Acta-Otolaryngol, 2002,122(1): 101-106.
31. Miyajima Y, Nakano R,Morimatsu M. Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization. Ann Otol Rhinol larygol, 1995,104(6):678-684.
32. Hoessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J, 1991,5(8):2145-2154.
33. Franchi A, Santucci M, Masini E, et al. Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck. Cancer, 2002, 95(9): 1902-1910.
34. Kataoka H, Tanaka H, Nagaike K, et al. Role of cancer cell-stroma interaction in invasive growth of cancer cells. Hum Cell. 2003,16(1):1-14.
35. Charous SJ, Stricklin GP, Nanney LB, et al. Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol, 1997,106(4): 271-278.
36. Krecicki T, Zalesska-Krecicka M, Jelen, et al. Expression of type Ⅳ collagen and matrix metalloproteinase-2 (type Ⅳ collagenase) in relation to nodal status in laryngeal cancer. Clin-Otolaryngol, 2001, 26(6): 469-472.
37. Ellis S, Nabeshima K, Biswas C. Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res, 1989,49(5):3385-3391.
38. Zucker S, Hymowitz M, Rollo EE, et al. Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol, 2001,158(6):1921-1928.
39. Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res, 2001,61(5):2276-2281.
40. Biswas C, Zhang Y, DeCastro R, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995,55(2):434-439.
41. Guo H, Majmudar G, Jensen T C , et al. Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of matrix metalloproteinases. Gene, 1998, 220(1-2): 99-108
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