• 上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院普外科(上海201900);

目的 　介紹基質(zhì)金屬蛋白酶(MMPs)在胃癌發(fā)生、發(fā)展中的作用。
方法 　收集近年來國內(nèi)、外有關(guān)MMPs與胃癌關(guān)系的文獻(xiàn)并作綜述。
結(jié)果 　胃癌的發(fā)生、發(fā)展是多步驟、多因素的復(fù)雜過程，其病因和發(fā)病機(jī)理仍未完全闡明。MMPs是一類蛋白水解酶，它們通過對腫瘤生長的微環(huán)境進(jìn)行調(diào)控,進(jìn)而在胃癌演進(jìn)中的增殖、轉(zhuǎn)移、新生血管形成和調(diào)控腫瘤細(xì)胞及其周圍正常細(xì)胞凋亡的過程中均起著重要的作用。
結(jié)論 　MMPs從不同的方面促進(jìn)胃癌的演進(jìn)，了解這些方面的機(jī)理可以為未來胃癌的治療提供理論依據(jù)。

引用本文： 江州華,俞繼衛(wèi),姜波健. 基質(zhì)金屬蛋白酶對胃癌微環(huán)境調(diào)控作用的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(9): 768-772. doi: 復(fù)制

1. 張鵬, 俞繼衛(wèi), 姜波健. 腫瘤干細(xì)胞與胃腸道癌發(fā)生和轉(zhuǎn)移 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2009; 16(1): 81-84.
2. Woessner JF Jr. MMPs and TIMPs－an historical perspective [Ｊ]. Mol Biotechnol, 2002; 22(1): 33-49.
3. McCawley LJ, Matrisian LM. Matrix metalloproteinases: th-ey’re not just for matrix anymore! [Ｊ]. Curr Opin Cell Biol, 2001; 13(5): 534-540.
4. Yu WH, Woessner JF Jr, McNeish JD, et al. CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling [Ｊ]. Genes Dev, 2002; 16(3): 307-323.
5. Suzuki M, Raab G, Moses MA, et al. Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site [Ｊ]. J Biol Chem, 1997; 272(50): 31730-31737.
6. Rauvala M, Aglund K, Puistola U, et al. Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression [Ｊ]. Int J Gynecol Cancer, 2006; 16(3): 1297-1302.
7. Tatti O, Vehvilinen P, Lehti K, et al. MT1-MMP releases latent TGF-beta1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1 [Ｊ]. Exp Cell Res, 2008； 314(13): 2501-2514.
8. Puthawala K, Hadjiangelis N, Jacoby SC, et al. Inhibition of integrin αvβ6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis [Ｊ]. Am J Respir Crit Care Med, 2008; 177(1): 82-90.
9. Miyamoto S, Nakamura M, Yano K, et al. Matrix metalloproteinase-7 triggers the matricrine action of insulin-like growth factor-Ⅱ via proteinase activity on insulin-like growth factor binding protein 2 in the extracellular matrix [Ｊ]. Cancer Sci, 2007; 98(5): 685-691.
10. Mysliwy J, Dingley AJ, Sedlacek R, et al. Structural characterization and binding properties of the hemopexin-like domain of the matrixmetalloproteinase-19 [Ｊ]. Protein Expr Purif, 2006; 46(2): 406-413.
11. Gennigens C, Menetrier-Caux C, Droz JP. Insulin-like gro-wth factor (IGF) family and prostate cancer [Ｊ]. Crit Rev Oncol Hematol, 2006; 58(2): 124-145.
12. Uttamsingh S, Bao X, Nguyen KT, et al. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells [Ｊ]. Oncogene, 2008; 27(18): 2626-2634.
13. Kwabi-Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer [Ｊ]. Endocr Relat Cancer, 2004; 11(4): 709-724.
14. Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [Ｊ]. Anticancer Res, 2006; 26(5A): 3579-3583.
15. Zheng HC, Sun JM, Li XH, et al. Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma [Ｊ]. Pathol Int, 2003; 53(10): 659-666.
16. Yasui W, Oue N, Aung PP, et al. Molecular-pathological prognostic factors of gastric cancer: a review [Ｊ]. Gastric Cancer, 2005; 8(2): 86-94.
17. Elnemr A, Yonemura Y, Bandou E, et al. Expression of collagenase-3 (matrix metalloproteinase-13) in human gastric cancer [Ｊ]. Gastric Cancer, 2003; 6(1): 30-38.
18. 嚴(yán)冬, 沈琳, 呂尤勇. MMP-11在胃癌患者血清中的表達(dá)及臨床意義 [Ｊ]. 中國癌癥雜志, 2007; 17(12): 968-972.
19. Friedl P, Brcker EB. The biology of cell locomotion within three-dimensional extracellular matrix [Ｊ]. Cell Mol Life Sci, 2000; 57(1): 41-64.
20. Dittmar T, Heyder C, Gloria-Maercker E, et al. Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner [Ｊ]. Clin Exp Metastasis, 2008; 25(1): 11-32.
21. Hornebeck W, Emonard H, Maquart FX, et al. Proteolysis directed by the extracellular matrix [Ｊ]. J Soc Biol, 2003; 197(1): 25-30.
22. Przybylo JA, Radisky DC. Matrix metalloproteinase-induced epithelial-mesenchymal transition: tumor progression at Snail’s pace [Ｊ]. Int J Biochem Cell Biol, 2007; 39(6): 1082-1088.
23. 徐勝軍, 胡炳奎, 凌志強(qiáng), 等. CD44v6在胃癌中的表達(dá)及其臨床意義 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(1): 42-44.
24. Giannelli G, Falk-Marzillier J, Schiraldi O, et al. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5 [Ｊ]. Science, 1997; 277(5323): 225-228.
25. Nisato RE, Hosseini G, Sirrenberg C, et al. Dissecting the role of matrix metalloproteinases (MMP) and integrin αvβ3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-type 1-MMP and αvβ3 are critical [Ｊ]. Cancer Res, 2005; 65(20): 9377-9387.
26. Deryugina EI, Soroceanu L, Strongin AY. Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis [Ｊ]. Cancer Res, 2002; 62(2): 580-588.
27. Dean RA, Butler GS, Hamma-Kourbali Y, et al. Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis [Ｊ]. Mol Cell Biol, 2007; 27(24): 8454-8465.
28. Hashimoto G, Inoki I, Fujii Y, et al. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165 [Ｊ]. J Biol Chem, 2002; 277(39): 36288-36295.
29. Ito TK, Ishii G, Chiba H, et al. The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells [Ｊ]. Oncogene, 2007; 26(51): 7194-7203.
30. Soff GA. Angiostatin and angiostatin-related proteins [Ｊ]. Cancer Metastasis Rev, 2000; 19(1-2): 97-107.
31. Pozzi A, LeVine WF, Gardner HA. Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis [Ｊ]. Oncogene, 2002; 21(2): 272-281.
32. Jodele S, Blavier L, Yoon JM, et al. Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression [Ｊ]. Cancer Metastasis Rev, 2006; 25(1): 35-43.
33. 俞繼衛(wèi), 姜波健. 胃癌浸潤和轉(zhuǎn)移中基質(zhì)金屬蛋白酶及其抑制劑的分子基礎(chǔ)和臨床價值 [Ｊ]. 腹部外科, 2007; 20(4): 245-247.
  1. 1. 張鵬, 俞繼衛(wèi), 姜波健. 腫瘤干細(xì)胞與胃腸道癌發(fā)生和轉(zhuǎn)移 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2009; 16(1): 81-84.
  2. 2. Woessner JF Jr. MMPs and TIMPs－an historical perspective [Ｊ]. Mol Biotechnol, 2002; 22(1): 33-49.
  3. 3. McCawley LJ, Matrisian LM. Matrix metalloproteinases: th-ey’re not just for matrix anymore! [Ｊ]. Curr Opin Cell Biol, 2001; 13(5): 534-540.
  4. 4. Yu WH, Woessner JF Jr, McNeish JD, et al. CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling [Ｊ]. Genes Dev, 2002; 16(3): 307-323.
  5. 5. Suzuki M, Raab G, Moses MA, et al. Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site [Ｊ]. J Biol Chem, 1997; 272(50): 31730-31737.
  6. 6. Rauvala M, Aglund K, Puistola U, et al. Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression [Ｊ]. Int J Gynecol Cancer, 2006; 16(3): 1297-1302.
  7. 7. Tatti O, Vehvilinen P, Lehti K, et al. MT1-MMP releases latent TGF-beta1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1 [Ｊ]. Exp Cell Res, 2008； 314(13): 2501-2514.
  8. 8. Puthawala K, Hadjiangelis N, Jacoby SC, et al. Inhibition of integrin αvβ6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis [Ｊ]. Am J Respir Crit Care Med, 2008; 177(1): 82-90.
  9. 9. Miyamoto S, Nakamura M, Yano K, et al. Matrix metalloproteinase-7 triggers the matricrine action of insulin-like growth factor-Ⅱ via proteinase activity on insulin-like growth factor binding protein 2 in the extracellular matrix [Ｊ]. Cancer Sci, 2007; 98(5): 685-691.
  10. 10. Mysliwy J, Dingley AJ, Sedlacek R, et al. Structural characterization and binding properties of the hemopexin-like domain of the matrixmetalloproteinase-19 [Ｊ]. Protein Expr Purif, 2006; 46(2): 406-413.
  11. 11. Gennigens C, Menetrier-Caux C, Droz JP. Insulin-like gro-wth factor (IGF) family and prostate cancer [Ｊ]. Crit Rev Oncol Hematol, 2006; 58(2): 124-145.
  12. 12. Uttamsingh S, Bao X, Nguyen KT, et al. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells [Ｊ]. Oncogene, 2008; 27(18): 2626-2634.
  13. 13. Kwabi-Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer [Ｊ]. Endocr Relat Cancer, 2004; 11(4): 709-724.
  14. 14. Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [Ｊ]. Anticancer Res, 2006; 26(5A): 3579-3583.
  15. 15. Zheng HC, Sun JM, Li XH, et al. Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma [Ｊ]. Pathol Int, 2003; 53(10): 659-666.
  16. 16. Yasui W, Oue N, Aung PP, et al. Molecular-pathological prognostic factors of gastric cancer: a review [Ｊ]. Gastric Cancer, 2005; 8(2): 86-94.
  17. 17. Elnemr A, Yonemura Y, Bandou E, et al. Expression of collagenase-3 (matrix metalloproteinase-13) in human gastric cancer [Ｊ]. Gastric Cancer, 2003; 6(1): 30-38.
  18. 18. 嚴(yán)冬, 沈琳, 呂尤勇. MMP-11在胃癌患者血清中的表達(dá)及臨床意義 [Ｊ]. 中國癌癥雜志, 2007; 17(12): 968-972.
  19. 19. Friedl P, Brcker EB. The biology of cell locomotion within three-dimensional extracellular matrix [Ｊ]. Cell Mol Life Sci, 2000; 57(1): 41-64.
  20. 20. Dittmar T, Heyder C, Gloria-Maercker E, et al. Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner [Ｊ]. Clin Exp Metastasis, 2008; 25(1): 11-32.
  21. 21. Hornebeck W, Emonard H, Maquart FX, et al. Proteolysis directed by the extracellular matrix [Ｊ]. J Soc Biol, 2003; 197(1): 25-30.
  22. 22. Przybylo JA, Radisky DC. Matrix metalloproteinase-induced epithelial-mesenchymal transition: tumor progression at Snail’s pace [Ｊ]. Int J Biochem Cell Biol, 2007; 39(6): 1082-1088.
  23. 23. 徐勝軍, 胡炳奎, 凌志強(qiáng), 等. CD44v6在胃癌中的表達(dá)及其臨床意義 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(1): 42-44.
  24. 24. Giannelli G, Falk-Marzillier J, Schiraldi O, et al. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5 [Ｊ]. Science, 1997; 277(5323): 225-228.
  25. 25. Nisato RE, Hosseini G, Sirrenberg C, et al. Dissecting the role of matrix metalloproteinases (MMP) and integrin αvβ3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-type 1-MMP and αvβ3 are critical [Ｊ]. Cancer Res, 2005; 65(20): 9377-9387.
  26. 26. Deryugina EI, Soroceanu L, Strongin AY. Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis [Ｊ]. Cancer Res, 2002; 62(2): 580-588.
  27. 27. Dean RA, Butler GS, Hamma-Kourbali Y, et al. Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis [Ｊ]. Mol Cell Biol, 2007; 27(24): 8454-8465.
  28. 28. Hashimoto G, Inoki I, Fujii Y, et al. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165 [Ｊ]. J Biol Chem, 2002; 277(39): 36288-36295.
  29. 29. Ito TK, Ishii G, Chiba H, et al. The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells [Ｊ]. Oncogene, 2007; 26(51): 7194-7203.
  30. 30. Soff GA. Angiostatin and angiostatin-related proteins [Ｊ]. Cancer Metastasis Rev, 2000; 19(1-2): 97-107.
  31. 31. Pozzi A, LeVine WF, Gardner HA. Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis [Ｊ]. Oncogene, 2002; 21(2): 272-281.
  32. 32. Jodele S, Blavier L, Yoon JM, et al. Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression [Ｊ]. Cancer Metastasis Rev, 2006; 25(1): 35-43.
  33. 33. 俞繼衛(wèi), 姜波健. 胃癌浸潤和轉(zhuǎn)移中基質(zhì)金屬蛋白酶及其抑制劑的分子基礎(chǔ)和臨床價值 [Ｊ]. 腹部外科, 2007; 20(4): 245-247.