Expressions of MT1-MMP and MMP-2 Protein in Papillary Thyroid Carcinoma and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUZhang-yi , TENGXu-yong , ZHANGHeng-wei , ZHANGLei , YUXing-en ,  LIUZhen

Department of The Pancreatic and Breast Surgery, Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China;

Corresponding author：

LIUZhen, Email: liuzhen1973@aliyun.com

Keywords：

Papillary thyroid carcinoma; Membrane type matrixmetalloproteinase-1; Matrix metalloproteinase-2; Capsule invasion; Metastasis

DOI：

10.7507/1007-9424.20150111

Video：

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Objective To investigate expressions and biological function of membrane type matrix metallopro-teinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in papillary thyroid carcinoma. Methods The expre-ssions of MT1-MMP and MMP-2 in 164 cases of papillary thyroid carcinoma and paracancerous tissues were detected by immunohistochemistry.The association between the expressions of MT1-MMP and MMP-2 and clinicopathological characteristics of papillary thyroid carcinoma was analyzed. Results In paracancerous tissues, the positive expression rate of MT1-MMP was 11.0% (18/164), and the positive expression rate of MMP-2 was 14.0% (23/164).In papillary thyroid carcinoma tissues, the positive expression rates of MT1-MMP and MMP-2 was 61.6% (101/164) and 67.7% (111/164), respectively.The expressions of MT1-MMP and MMP-2 in carcinoma tissues and para carcinoma tissues were statistically significant differences (P < 0.05).The expressions of MT1-MMP and MMP-2 in papillary thyroid carcinoma tissues correlated with the lymph node metastasis (P < 0.05).In addition, the expression of MMP-2 in papillary thyroid carcinoma tissues correlated with capsule invasion (P < 0.05).The positive correlation was found between the expressions of MT1-MMP and MMP-2 in papillary thyroid carcinoma tissues (r=0.256, P < 0.05). Conclusions MT1-MMP and MMP-2 may be involved the thyroid capsule invasion and lymph node metastasis of papillary thyroid carcinoma.MT1-MMP and MMP-2 may be involved in the progression of papillary thyroid carcinoma.

Citation： LIUZhang-yi, TENGXu-yong, ZHANGHeng-wei, ZHANGLei, YUXing-en, LIUZhen. Expressions of MT1-MMP and MMP-2 Protein in Papillary Thyroid Carcinoma and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(4): 418-422. doi: 10.7507/1007-9424.20150111 Copy

1.	Sun M, Fang S, Li W, Li C, et al.Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma.Cancer Biomark, 2015, 15(1):33-40.
2.	Park CS, Kim SH, Jung SL, et al.Observer variability in the sonographic evaluation of thyroid nodules.J Clin Ultrasound, 2010, 38(6):287-293.
3.	Li QS, Chen SH, Xiong HH, et al.Papillary thyroid carcinoma on sonography.Clin Imaging, 2010, 34(2):121-126.
4.	Jun HH, Kim SM, Kim BW, et al.Overcoming the limitations of fine needle aspiration biopsy:detection of lateral neck node metastasis in papillary thyroid carcinoma.Yonsei Med J, 2015, 56(1):182-188.
5.	Clark OH.Thyroid cancer and lymph node metastases.J Surg Oncol, 2011, 103(6):615-618.
6.	Yadav L, Puri N, Rastogi V, et al.Matrix metalloproteinases and cancer-roles in threat and therapy.Asian Pac J Cancer Prev, 2014, 15(3):1085-1091.
7.	Fink K, Boratyński J.The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis.Postepy Hig Med Dosw (Online), 2012, 66:609-628.
8.	Nagase H, Visse R, Murphy G.Structure and function of matrix metalloproteinases and TIMPs.Cardiovasc Res, 2006, 69(3):562-573.
9.	Gialeli C, Theocharis AD, Karamanos NK.Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.FEBS J, 2011, 278(1):16-27.
10.	Guo JQ, Zheng QH, Chen H, et al.Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE-cadherin/EphA2/MMP9/MMP2 expression.Int J Oncol, 2014, 45(3):1065-1072.
11.	Lovaas JD, Zhu L, Chiao CY, et al.SIRT1 enhances matrix metalloproteinase-2 expression and tumor cell invasion in prostate cancer cells.Prostate, 2013, 73(5):522-530.
12.	Bae GY, Choi SJ, Lee JS, et al.Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via the ZEB1/MMP2 axis in non-small cell lung cancer.Oncotarget, 2013, 4(12):2512-2522.
13.	Uraoka N, Oue N, Sakamoto N, et al.NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.Cancer Sci, 2014, 105(1):134-140.
14.	Grelewski PG, Bar JK.The role of p53 protein and MMP-2 tumor/ stromal cells expression on progressive growth of ovarian neoplasms.Cancer Invest, 2013, 31(7):472-479.
15.	Jacob A, Jing J, Lee J, et al.Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells.J Cell Sci, 2013, 126(Pt 20):4647-4658.
16.	Maquoi E, Frankenne F, Baramova E, et al.Membrane type 1 matrix metalloproteinase-associated degradation of tissue inhibitor of metalloproteinase 2 in human tumor cell lines.J Biol Chem, 2000, 275(15):11368-11378.
17.	Deryugina EI, Ratnikov B, Monosov E, et al.MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells.Exp Cell Res, 2001, 263(2):209-223.
18.	Hess AR, Seftor EA, Seftor RE, et al.Phosphoinositide 3-kinase regulates membrane type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry.Cancer Res, 2003, 63(16):4757-4762.
19.	Sood AK, Fletcher MS, Coffin JE, et al.Functional role of matrix metalloproteinases in ovarian tumor cell plasticity.Am J Obstet Gynecol, 2004, 190(4):899-909.
20.	刘臻, 滕绪永, 张恒玮, 等.甲状腺乳头状癌组织中MMP-9、趋化因子受体CXCR7表达的生物学意义.现代肿瘤医学, 2014, 22(4):802-805.
21.	Rahman MA, Dhar DK, Yamaguchi E, et al.Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver:possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases.Clin Cancer Res, 2001, 7(5):1325-1332.
22.	Saffar H, Sanii S, Emami B, et al.Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors.Pathol Res Pract, 2013, 209(3):195-199.
23.	Wu G, Zhou Y, Li T, et al.Immunohistochemical levels of matrix metalloproteinase-2 and CD44 variant 6 protein in the diagnosis and lateral cervical lymph node metastasis of papillary thyroid carcinoma.J Int Med Res, 2013, 41(3):816-824.
24.	Sato H, Takino T, Okada Y, et al.A matrix metalloproteinase expressed on the surface of invasive tumor cells.Nature, 1994, 370(1):61-65.
25.	Ip YC, Cheung ST, Leung KL, et al.Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma.World J Gastroenterol, 2005, 11(40):6269-6276.
26.	Mimori K, Fukagawa T, Kosaka Y, et al.A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.Ann Surg Oncol, 2008, 15(10):2934-2942.
27.	Perentes JY, Kirkpatrick ND, Nagano S, et al.Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors.Cancer Res, 2011, 71(13):4527-4538.
28.	Yao G, He P, Chen L, et al.MT1-MMP in breast cancer:induction of VEGF-C correlates with metastasis and poor prognosis.Cancer Cell Int, 2013, 13(1):98.

1. Sun M, Fang S, Li W, Li C, et al.Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma.Cancer Biomark, 2015, 15(1):33-40.
2. Park CS, Kim SH, Jung SL, et al.Observer variability in the sonographic evaluation of thyroid nodules.J Clin Ultrasound, 2010, 38(6):287-293.
3. Li QS, Chen SH, Xiong HH, et al.Papillary thyroid carcinoma on sonography.Clin Imaging, 2010, 34(2):121-126.
4. Jun HH, Kim SM, Kim BW, et al.Overcoming the limitations of fine needle aspiration biopsy:detection of lateral neck node metastasis in papillary thyroid carcinoma.Yonsei Med J, 2015, 56(1):182-188.
5. Clark OH.Thyroid cancer and lymph node metastases.J Surg Oncol, 2011, 103(6):615-618.
6. Yadav L, Puri N, Rastogi V, et al.Matrix metalloproteinases and cancer-roles in threat and therapy.Asian Pac J Cancer Prev, 2014, 15(3):1085-1091.
7. Fink K, Boratyński J.The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis.Postepy Hig Med Dosw (Online), 2012, 66:609-628.
8. Nagase H, Visse R, Murphy G.Structure and function of matrix metalloproteinases and TIMPs.Cardiovasc Res, 2006, 69(3):562-573.
9. Gialeli C, Theocharis AD, Karamanos NK.Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.FEBS J, 2011, 278(1):16-27.
10. Guo JQ, Zheng QH, Chen H, et al.Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE-cadherin/EphA2/MMP9/MMP2 expression.Int J Oncol, 2014, 45(3):1065-1072.
11. Lovaas JD, Zhu L, Chiao CY, et al.SIRT1 enhances matrix metalloproteinase-2 expression and tumor cell invasion in prostate cancer cells.Prostate, 2013, 73(5):522-530.
12. Bae GY, Choi SJ, Lee JS, et al.Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via the ZEB1/MMP2 axis in non-small cell lung cancer.Oncotarget, 2013, 4(12):2512-2522.
13. Uraoka N, Oue N, Sakamoto N, et al.NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.Cancer Sci, 2014, 105(1):134-140.
14. Grelewski PG, Bar JK.The role of p53 protein and MMP-2 tumor/ stromal cells expression on progressive growth of ovarian neoplasms.Cancer Invest, 2013, 31(7):472-479.
15. Jacob A, Jing J, Lee J, et al.Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells.J Cell Sci, 2013, 126(Pt 20):4647-4658.
16. Maquoi E, Frankenne F, Baramova E, et al.Membrane type 1 matrix metalloproteinase-associated degradation of tissue inhibitor of metalloproteinase 2 in human tumor cell lines.J Biol Chem, 2000, 275(15):11368-11378.
17. Deryugina EI, Ratnikov B, Monosov E, et al.MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells.Exp Cell Res, 2001, 263(2):209-223.
18. Hess AR, Seftor EA, Seftor RE, et al.Phosphoinositide 3-kinase regulates membrane type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry.Cancer Res, 2003, 63(16):4757-4762.
19. Sood AK, Fletcher MS, Coffin JE, et al.Functional role of matrix metalloproteinases in ovarian tumor cell plasticity.Am J Obstet Gynecol, 2004, 190(4):899-909.
20. 刘臻, 滕绪永, 张恒玮, 等.甲状腺乳头状癌组织中MMP-9、趋化因子受体CXCR7表达的生物学意义.现代肿瘤医学, 2014, 22(4):802-805.
21. Rahman MA, Dhar DK, Yamaguchi E, et al.Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver:possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases.Clin Cancer Res, 2001, 7(5):1325-1332.
22. Saffar H, Sanii S, Emami B, et al.Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors.Pathol Res Pract, 2013, 209(3):195-199.
23. Wu G, Zhou Y, Li T, et al.Immunohistochemical levels of matrix metalloproteinase-2 and CD44 variant 6 protein in the diagnosis and lateral cervical lymph node metastasis of papillary thyroid carcinoma.J Int Med Res, 2013, 41(3):816-824.
24. Sato H, Takino T, Okada Y, et al.A matrix metalloproteinase expressed on the surface of invasive tumor cells.Nature, 1994, 370(1):61-65.
25. Ip YC, Cheung ST, Leung KL, et al.Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma.World J Gastroenterol, 2005, 11(40):6269-6276.
26. Mimori K, Fukagawa T, Kosaka Y, et al.A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.Ann Surg Oncol, 2008, 15(10):2934-2942.
27. Perentes JY, Kirkpatrick ND, Nagano S, et al.Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors.Cancer Res, 2011, 71(13):4527-4538.
28. Yao G, He P, Chen L, et al.MT1-MMP in breast cancer:induction of VEGF-C correlates with metastasis and poor prognosis.Cancer Cell Int, 2013, 13(1):98.

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Expressions of MT1-MMP and MMP-2 Protein in Papillary Thyroid Carcinoma and Its Clinical Significance

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