Expression of ADAM9 in Breast Cancer and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIAN Hongmei ^1,2 , LI Junsheng ¹ , ZHANG Yanan ¹ , WEI Xiaoying ³ , JI Zhenling ¹

1.Department of General Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, China;;
2.Department of General Surgery, Ma’anshan Municipal People’s Hospital, Ma’anshan 243000, Anhui Province, China;;
3.Department of Pathology, Zhongda Hospital, Southeast University, Nanjing 210009, China;

Corresponding author：

Keywords：

Breast cancer; A disintegrin and metalloproteinase 9; Reverse transcription polymerase chain reaction; Immunohistochemistry

Video：

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Objective To investigate the expression of ADAM9 in breast cancer and its clinical significance.
Methods The expressions of ADAM9 in normal breast tissues and breast cancer tissues were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, and whose relationship with clinicopathologic features was analyzed.
Results The expression of ADAM9 mRNA increased in the breast cancer tissues, but which was not detected in the normal breast tissues. The expression of ADAM9 protein in the breast cancer tissues was significantly higher than that in the normal breast tissues (P lt;0.05), and which in the metastatic lymph nodes was significantly higher than that in the negative lymph nodes or corresponding primary lesions (P lt;0.05). The expression of ADAM9 in the breast cancer tissues was correlated with the lymph node metastasis and histological grade (P lt;0.05). Conclusion ADAM9 is overexpressed in the breast cancer tissues, which might involve in the pathological progression of breast cancer.

Citation： QIAN Hongmei ,LI Junsheng,ZHANG Yanan,WEI Xiaoying,JI Zhenling. Expression of ADAM9 in Breast Cancer and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(9): 927-931. doi: Copy

1.	Jemal A, Siegel R, Ward E, et al. Cancer satistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 225249.
2.	上海市疾病预防控制中心. 2006年上海市市区恶性肿瘤发病率 [J]. 肿瘤, 2009; 29(9): 918.
3.	Peduto L, Reuter VE, Shaffer DR, et al. Critical function for ADAM9 in mouse prostate cancer [J]. Cancer Res, 2005; 65(20): 93129319.
4.	Grützmann R, Lüttges J, Sipos B, et al. ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma [J]. Br J Cancer, 2004; 90(5): 10531058.
5.	Hirao T, Nanba D, Tanaka M, et al. Overexpression of ADAM9 enhances growth factormediated recycling of Ecadherin in human colon cancer cell line HT29 cells [J]. Exp Cell Res, 2006; 312(3): 331339.
6.	Zigrino P, Mauch C, Fox JW, et al. Adam9 expression and regulation in human skin melanoma and melanoma cell lines [J]. Int J Cancer, 2005; 116(6): 853859.
7.	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2007版) [J]. 中国癌症杂志, 2007; 17(5): 410429.
8.	Parham DM. Mitotic activity and histological grading of breast cancer [J]. Pathol Annu, 1995; 30(Pt 1): 189207.
9.	施文, 李俊生. 结肠癌组织中ADAM9的表达及其与微血管密度的关系 [J]. 东南大学学报（医学版）， 2009; 28(4): 274277.
10.	Schwettmann L, Tschesche H. Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin [J]. Protein Expr Purif, 2001; 21(1): 6570.
11.	Nath D, Slocombe PM, Webster A, et al. Meltrin γ (ADAM9) mediates cellular adhesion through α6β1 integrin, leading to a marked induction of fibroblast cell motility [J]. J Cell Sci, 2000; 113(Pt 12): 23192328.
12.	Karadag A, Zhou M, Croucher PI. ADAM9 (MDC9/meltrinγ), a member of the a disintegrin and metalloproteinase family, regulates myelomacellinduced interleukin6 production in osteoblasts by direct interaction with the αⅤβ5 integrin [J]. Blood, 2006; 107(8): 32713278.
13.	Zigrino P, Steiger J, Fox JW, et al. Role of ADAM9 disintegrincysteinerich domains in human keratinocyte migration [J]. J Biol Chem, 2007; 282(42): 3078530793.
14.	Mazzocca A, Coppari R, De Franco R, et al. A secreted form of ADAM9 promotes carcinoma invasion through tumorstromal interactions [J]. Cancer Res, 2005; 65(11): 47284738.
15.	Shintani Y, Higashiyama S, Ohta M, et al. Overexpression of ADAM9 in nonsmall cell lung cancer correlates with brain metastasis [J]. Cancer Res, 2004; 64(12): 41904196.
16.	Sung SY, Kubo H, Shigemura K, et al. Oxidative stress induces ADAM9 protein expression in human prostate cancer cells [J]. Cancer Res, 2006; 66(19): 95199526.
17.	Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J]. Cancer Cell, 2006; 10(6): 529541.
18.	CarlMcGrath S, Lendeckel U, Ebert M, et al.The disintegrinmetalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer [J]. Int J Oncol, 2005; 26(1): 1724.
19.	Johnstone P, Sung S, Anderson C, et al. The natural product honokiol potentiates radiation sensitization induced by SiRNA ADAM9 knockdown in prostate cancer cells [J]. Radiother Oncol, 2006; 78: S76S77.
20.	Weskamp G, Cai H, Brodie TA, et al. Mice lacking the metalloproteasedisintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life [J]. Mol Cell Biol, 2002; 22(5): 15371544.
21.	O’Shea C, McKie N, Buggy Y, et al. Expression of ADAM9 mRNA and protein in human breast cancer [J]. Int J Cancer, 2003； 105(6): 754761.
22.	Park D, Kresen R, Noren T, et al. Ki67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications[J]. Virchows Arch, 2007; 451(1): 1118.
23.	Shim H, Lau SK, Devi S, et al. Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by liganddependent degradation and HIF1α [J]. Biochem Biophys Res Commun, 2006; 346(1): 252258.
24.	Goedheer AJ, Portengen H, Klijn JG, et al. How ADAM9 and ADAM11 differentially from estrogen receptor predict response to tamoxifen treatment in patients with recurrent breast cancer: a retrospective study [J]. Clin Cancer Res, 2005； 11(20): 73117321.
25.	Fritzsche FR, Wassermann K, Jung M, et al. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression [J]. BMC Cancer, 2008； 8: 179187.

1. Jemal A, Siegel R, Ward E, et al. Cancer satistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 225249.
2. 上海市疾病预防控制中心. 2006年上海市市区恶性肿瘤发病率 [J]. 肿瘤, 2009; 29(9): 918.
3. Peduto L, Reuter VE, Shaffer DR, et al. Critical function for ADAM9 in mouse prostate cancer [J]. Cancer Res, 2005; 65(20): 93129319.
4. Grützmann R, Lüttges J, Sipos B, et al. ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma [J]. Br J Cancer, 2004; 90(5): 10531058.
5. Hirao T, Nanba D, Tanaka M, et al. Overexpression of ADAM9 enhances growth factormediated recycling of Ecadherin in human colon cancer cell line HT29 cells [J]. Exp Cell Res, 2006; 312(3): 331339.
6. Zigrino P, Mauch C, Fox JW, et al. Adam9 expression and regulation in human skin melanoma and melanoma cell lines [J]. Int J Cancer, 2005; 116(6): 853859.
7. 中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2007版) [J]. 中国癌症杂志, 2007; 17(5): 410429.
8. Parham DM. Mitotic activity and histological grading of breast cancer [J]. Pathol Annu, 1995; 30(Pt 1): 189207.
9. 施文, 李俊生. 结肠癌组织中ADAM9的表达及其与微血管密度的关系 [J]. 东南大学学报（医学版）， 2009; 28(4): 274277.
10. Schwettmann L, Tschesche H. Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin [J]. Protein Expr Purif, 2001; 21(1): 6570.
11. Nath D, Slocombe PM, Webster A, et al. Meltrin γ (ADAM9) mediates cellular adhesion through α6β1 integrin, leading to a marked induction of fibroblast cell motility [J]. J Cell Sci, 2000; 113(Pt 12): 23192328.
12. Karadag A, Zhou M, Croucher PI. ADAM9 (MDC9/meltrinγ), a member of the a disintegrin and metalloproteinase family, regulates myelomacellinduced interleukin6 production in osteoblasts by direct interaction with the αⅤβ5 integrin [J]. Blood, 2006; 107(8): 32713278.
13. Zigrino P, Steiger J, Fox JW, et al. Role of ADAM9 disintegrincysteinerich domains in human keratinocyte migration [J]. J Biol Chem, 2007; 282(42): 3078530793.
14. Mazzocca A, Coppari R, De Franco R, et al. A secreted form of ADAM9 promotes carcinoma invasion through tumorstromal interactions [J]. Cancer Res, 2005; 65(11): 47284738.
15. Shintani Y, Higashiyama S, Ohta M, et al. Overexpression of ADAM9 in nonsmall cell lung cancer correlates with brain metastasis [J]. Cancer Res, 2004; 64(12): 41904196.
16. Sung SY, Kubo H, Shigemura K, et al. Oxidative stress induces ADAM9 protein expression in human prostate cancer cells [J]. Cancer Res, 2006; 66(19): 95199526.
17. Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J]. Cancer Cell, 2006; 10(6): 529541.
18. CarlMcGrath S, Lendeckel U, Ebert M, et al.The disintegrinmetalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer [J]. Int J Oncol, 2005; 26(1): 1724.
19. Johnstone P, Sung S, Anderson C, et al. The natural product honokiol potentiates radiation sensitization induced by SiRNA ADAM9 knockdown in prostate cancer cells [J]. Radiother Oncol, 2006; 78: S76S77.
20. Weskamp G, Cai H, Brodie TA, et al. Mice lacking the metalloproteasedisintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life [J]. Mol Cell Biol, 2002; 22(5): 15371544.
21. O’Shea C, McKie N, Buggy Y, et al. Expression of ADAM9 mRNA and protein in human breast cancer [J]. Int J Cancer, 2003； 105(6): 754761.
22. Park D, Kresen R, Noren T, et al. Ki67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications[J]. Virchows Arch, 2007; 451(1): 1118.
23. Shim H, Lau SK, Devi S, et al. Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by liganddependent degradation and HIF1α [J]. Biochem Biophys Res Commun, 2006; 346(1): 252258.
24. Goedheer AJ, Portengen H, Klijn JG, et al. How ADAM9 and ADAM11 differentially from estrogen receptor predict response to tamoxifen treatment in patients with recurrent breast cancer: a retrospective study [J]. Clin Cancer Res, 2005； 11(20): 73117321.
25. Fritzsche FR, Wassermann K, Jung M, et al. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression [J]. BMC Cancer, 2008； 8: 179187.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of ADAM9 in Breast Cancer and Its Clinical Significance

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