Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines

Oncotarget

Volumn 6, Issue 6, 2015, Pages 3932-3946

  Momeny, Majid ^a   Saunus, Jodi M ^a,b   Marturana, Flavia ^a   McCart Reed, Amy E ^a,b   Black, Debra ^a,b   Sala, Gianluca ^c   Iacobelli, Stefano ^c   Holland, Jane D ^d   Yu, Dihua ^e   Da Silva, Leonard ^a,g   Simpson, Peter T ^a,b,g   Khanna, Kum Kum ^b   Chenevix Trench, Georgia ^b   Lakhani, Sunil R ^a,f,g  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^c Mediapharma srl   (Italy)

^d MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^e UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^f ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

^g UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Blood brain barrier; Breast cancer brain metastases; HER2; HER3; Heregulin; Matrix metalloproteinase

Indexed keywords

CATHEPSIN B; CYCLIN D1; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; EV 20; GELATINASE B; HUMAN MONOCLONAL ANTIBODY; INTERCELLULAR ADHESION MOLECULE 1; NEU DIFFERENTIATION FACTOR; PROTEIN P27; TRASTUZUMAB; UNCLASSIFIED DRUG; ERBB2 PROTEIN, HUMAN; ERBB3 PROTEIN, HUMAN; GELATINASE A; NRG1 PROTEIN, HUMAN;

ARTICLE; BLOOD BRAIN BARRIER; BREAST CANCER; CANCER CELL LINE; CAPILLARY ENDOTHELIAL CELL; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; HUMAN; HUMAN CELL; IN VITRO STUDY; METASTASIS; SIGNAL TRANSDUCTION; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION; TUMOR MICROENVIRONMENT; BRAIN; BREAST TUMOR; CELL MOTION; ENDOTHELIUM CELL; ENZYMOLOGY; FEMALE; GENETICS; MCF-7 CELL LINE; METABOLISM; PATHOLOGY; PHYSIOLOGY; TUMOR CELL LINE; VASCULARIZATION;

BLOOD-BRAIN BARRIER; BRAIN; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL MOVEMENT; ENDOTHELIAL CELLS; FEMALE; HUMANS; MATRIX METALLOPROTEINASE 2; MATRIX METALLOPROTEINASE 9; MCF-7 CELLS; NEUREGULIN-1; RECEPTOR, ERBB-2; RECEPTOR, ERBB-3; SIGNAL TRANSDUCTION;

EID: 84924239319     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2846     Document Type: Article

References (83)

1. Fox BD, Cheung VJ, Patel AJ, Suki D, Rao G. Epidemiology of metastatic brain tumors. Neurosurg Clin N Am. 2011; 22:1-6, v.
2. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004; 22:2865-2872.
3. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004; 22:3608-3617.
4. Harrell JC, Prat A, Parker JS, Fan C, He X, Carey L, Anders C, Ewend M, Perou CM. Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse. Breast Cancer Res Treat. 2011.
5. Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, Crivellari D, Fey MF, Murray E, Pagani O, Simoncini E, Castiglione-Gertsch M, Gelber RD, Coates AS, Goldhirsch A. International Breast Cancer Study G: Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006; 17:935-944.
6. Lin NU, Amiri-Kordestani L, Palmieri D, Liewehr DJ, Steeg PS. CNS metastases in breast cancer: old challenge, new frontiers. Clin Cancer Res. 2013; 19:6404-6418.
7. Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011; 17:4834-4843.
8. Swain SM, Baselga J, Miles D, Im YH, Quah C, Lee LF, Cortes J. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014; 25:1116-1121.
9. Bartsch R, Berghoff A, Pluschnig U, Bago-Horvath Z, Dubsky P, Rottenfusser A, DeVries C, Rudas M, Fitzal F, Dieckmann K, Mader RM, Gnant M, Zielinski CC, Steger GG. Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Br J Cancer. 2012; 106:25-31.
10. Park YH, Park MJ, Ji SH, Yi SY, Lim DH, Nam DH, Lee JI, Park W, Choi DH, Huh SJ, Ahn JS, Kang WK, Park K, Im YH. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer. 2009; 100:894-900.
11. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, Sliwkowski MX, Stern HM. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008; 68:5878-5887.
12. Campiglio M, Ali S, Knyazev PG, Ullrich A. Characteristics of EGFR family-mediated HRG signals in human ovarian cancer. J Cell Biochem. 1999; 73:522-532.
13. Zhang Y, Opresko L, Shankaran H, Chrisler WB, Wiley HS, Resat H. HER/ErbB receptor interactions and signaling patterns in human mammary epithelial cells. BMC Cell Biol. 2009; 10:78.
14. Ueno Y, Sakurai H, Tsunoda S, Choo MK, Matsuo M, Koizumi K, Saiki I. Heregulin-induced activation of ErbB3 by EGFR tyrosine kinase activity promotes tumor growth and metastasis in melanoma cells. Int J Cancer. 2008; 123:340-347.
15. Garrett JT, Olivares MG, Rinehart C, Granja-Ingram ND, Sanchez V, Chakrabarty A, Dave B, Cook RS, Pao W, McKinely E, Manning HC, Chang J, Arteaga CL. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. PNAS. 2011; 108:5021-5026.
16. Vaught DB, Stanford JC, Young C, Hicks DJ, Wheeler F, Rinehart C, Sanchez V, Koland J, Muller WJ, Arteaga CL, Cook RS. HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation. Cancer Res. 2012; 72:2672-2682.
17. Eccles SA. The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis. J Mammary Gland Biol Neoplasia. 2001; 6:393-406.
18. Bernstein HG, Lendeckel U, Bertram I, Bukowska A, Kanakis D, Dobrowolny H, Stauch R, Krell D, Mawrin C, Budinger E, Keilhoff G, Bogerts B. Localization of neuregulin-1alpha (heregulin-alpha) and one of its receptors, ErbB-4 tyrosine kinase, in developing and adult human brain. Brain Res Bull. 2006; 69:546-559.
19. Pinkas-Kramarski R, Eilam R, Spiegler O, Lavi S, Liu N, Chang D, Wen D, Schwartz M, Yarden Y. Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes. PNAS. 1994; 91:9387-9391.
20. Lok J, Sardi SP, Guo S, Besancon E, Ha DM, Rosell A, Kim WJ, Corfas G, Lo EH. Neuregulin-1 signaling in brain endothelial cells. J Cereb Blood Flow Metab. 2009; 29:39-43.
21. Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol. 2007; 190:1-65.
22. Berghoff AS, Bartsch R, Preusser M, Ricken G, Steger GG, Bago-Horvath Z, Rudas M, Streubel B, Dubsky P, Gnant M, Fitzal F, Zielinski CC, Birner P. Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients. Breast. 2014; 23:637-643.
23. Da Silva L, Simpson PT, Smart CE, Cocciardi S, Waddell N, Lane A, Morrison BJ, Vargas A, Healey S, Beesley J, Pakkiri P, Parry S, Kurniawan N, Reid L, Keith P, Faria P, et al. HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer. Breast Cancer Res. 2010; 12:R46.
24. Sun M, Behrens C, Feng L, Ozburn N, Tang X, Yin G, Komaki R, Varella-Garcia M, Hong WK, Aldape KD, Wistuba II. HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res. 2009; 15:4829-4837.
25. Yu D, Hamada J, Zhang H, Nicolson GL, Hung MC. Mechanisms of c-erbB2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. Oncogene. 1992; 7:2263-2270.
26. Asrani K, Keri RA, Galisteo R, Brown SA, Morgan SJ, Ghosh A, Tran NL, Winkles JA. The HER2-and heregulin beta1 (HRG)-inducible TNFR superfamily member Fn14 promotes HRG-driven breast cancer cell migration, invasion, and MMP9 expression. Mol Cancer Res. 2013; 11:393-404.
27. Yao J, Xiong S, Klos K, Nguyen N, Grijalva R, Li P, Yu D. Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells. Oncogene. 2001; 20:8066-8074.
28. Xu FJ, Stack S, Boyer C, O'Briant K, Whitaker R, Mills GB, Yu YH, Bast RC, Jr. Heregulin and agonistic anti-p185(c-erbB2) antibodies inhibit proliferation but increase invasiveness of breast cancer cells that overexpress p185(c-erbB2): increased invasiveness may contribute to poor prognosis. Clin Cancer Res. 1997; 3:1629-1634.
29. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010; 141:52-67.
30. Figueira RC, Gomes LR, Neto JS, Silva FC, Silva ID, Sogayar MC. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer. 2009; 9:20.
31. Mendes O, Kim HT, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis. 2005; 22:237-246.
32. Mendes O, Kim HT, Lungu G, Stoica G. MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2. Clin Exp Metastasis. 2007; 24:341-351.
33. Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchran R. Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One. 2013; 8:e80933.
34. Lee KY, Kim YJ, Yoo H, Lee SH, Park JB, Kim HJ. Human brain endothelial cell-derived COX-2 facilitates extravasation of breast cancer cells across the blood-brain barrier. Anticancer Res. 2011; 31:4307-4313.
35. Liu H, Kato Y, Erzinger SA, Kiriakova GM, Qian Y, Palmieri D, Steeg PS, Price JE. The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer. 2012; 12:583.
36. Stark AM, Anuszkiewicz B, Mentlein R, Yoneda T, Mehdorn HM, Held-Feindt J. Differential expression of matrix metalloproteinases in brain-and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells. J Neurooncol. 2007; 81:39-48.
37. Tester AM, Waltham M, Oh SJ, Bae SN, Bills MM, Walker EC, Kern FG, Stetler-Stevenson WG, Lippman ME, Thompson EW. Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice. Cancer Res. 2004; 64:652-658.
38. Pardridge WM. Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv. 2003; 3:90-105, 151.
39. Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. 2011; 8:344-356.
40. Fidler IJ, Balasubramanian K, Lin Q, Kim SW, Kim SJ. The brain microenvironment and cancer metastasis. Mol Cells. 2010; 30:93-98.
41. Neman J, Choy C, Kowolik CM, Anderson A, Duenas VJ, Waliany S, Chen BT, Chen MY, Jandial R. Co-evolution of breast-to-brain metastasis and neural progenitor cells. Clin Exp Metastasis. 2013; 30:753-768.
42. Neman J, Termini J, Wilczynski S, Vaidehi N, Choy C, Kowolik CM, Li H, Hambrecht AC, Roberts E, Jandial R. Human breast cancer metastases to the brain display GABAergic properties in the neural niche. PNAS. 2014; 111:984-989.
43. Termini J, Neman J, Jandial R. Role of the neural niche in brain metastatic cancer. Cancer Res. 2014; 74:4011-4015.
44. Hollestelle A, Nagel JHA, Smid M, Lam S, Elstrodt F, Wasielewski M, Ng SS, French PJ, Peeters JK, Rozendaal MJ, Riaz M, Koopman DG, ten Hagen TLM, Leeuw BHCGM, Zwarthoff EC, Teunisse A, et al. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res Treat. 2009; 121:53-64.
45. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe J-P, Tong F. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006; 10:515-527.
46. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast cancer research: BCR. 2010; 12:R68.
47. Zhang RD, Fidler IJ, Price JE. Relative malignant potential of human breast carcinoma cell lines established from pleural effusions and a brain metastasis. Invasion Metastasis. 1991; 11:204-215.
48. Bergman I, Barmada MA, Griffin JA, Slamon DJ. Treatment of meningeal breast cancer xenografts in the rat using an anti-p185/HER2 antibody. Clin Cancer Res. 2001; 7:2050-2056.
49. Hijazi MM, Thompson EW, Tang C, Coopman P, Torri JA, Yang D, Mueller SC, Lupu R. Heregulin regulates the actin cytoskeleton and promotes invasive properties in breast cancer cell lines. Int J Oncol. 2000; 17:629-641.
50. Kim J, Jeong H, Lee Y, Kim C, Kim H, Kim A. HRG-beta1-driven ErbB3 signaling induces epithelial-mesenchymal transition in breast cancer cells. BMC Cancer. 2013; 13:383.
51. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, Gili M, Russillo M, Parra JL, Singh S, Arribas J, Rosen N, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene. 2011; 30:2547-2557.
52. Lenferink AE, Busse D, Flanagan WM, Yakes FM, Arteaga CL. ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple signaling pathways. Cancer Res. 2001; 61:6583-6591.
53. Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol. 1993; 4:219-229.
54. Soto MS, Serres S, Anthony DC, Sibson NR. Functional role of endothelial adhesion molecules in the early stages of brain metastasis. Neuro Oncol. 2014; 16:540-551.
55. Arshad F, Wang L, Sy C, Avraham S, Avraham HK. Blood-brain barrier integrity and breast cancer metastasis to the brain. Pathology research international. 2010; 2011:920509.
56. Roland CL, Harken AH, Sarr MG, Barnett CC, Jr. ICAM-1 expression determines malignant potential of cancer. Surgery. 2007; 141:705-707.
57. Regidor PA, Callies R, Regidor M, Schindler AE. Expression of the cell adhesion molecules ICAM-1 and VCAM-1 in the cytosol of breast cancer tissue, benign breast tissue and corresponding sera. Eur J Gynaecol Oncol. 1998; 19:377-383.
58. Rosette C, Roth RB, Oeth P, Braun A, Kammerer S, Ekblom J, Denissenko MF. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis. 2005; 26:943-950.
59. Sollome JJ, Thavathiru E, Camenisch TD, Vaillancourt RR. HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4). Cell Signal. 2014; 26:70-82.
60. Ruan SQ, Wang ZH, Wang SW, Fu ZX, Xu KL, Li DB, Zhang SZ. Heregulin-beta1-induced GPR30 upregulation promotes the migration and invasion potential of SkBr3 breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway. Biochem Biophys Res Commun. 2012; 420:385-390.
61. Lazaro G, Smith C, Goddard L, Jordan N, McClelland R, Barrett-Lee P, Nicholson RI, Hiscox S. Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response. Endocr Relat Cancer. 2013; 20:691-704.
62. Shukla S, Maclennan GT, Hartman DJ, Fu P, Resnick MI, Gupta S. Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer. 2007; 121:1424-1432.
63. Wikman H, Westphal L, Schmid F, Pollari S, Kropidlowski J, Sielaff-Frimpong B, Glatzel M, Matschke J, Westphal M, Iljin K, Huhtala H, Terracciano L, Kallioniemi A, Sauter G, Muller V, Witzel I, et al. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. Oncotarget. 2014; 5:3076-3087.
64. Jee BK, Park KM, Surendran S, Lee WK, Han CW, Kim YS, Lim Y. KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochem Biophys Res Commun. 2006; 342:655-661.
65. Hong KJ, Hsu MC, Hou MF, Hung WC. The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling. FEBS Lett. 2011; 585:591-595.
66. Rafn B, Nielsen CF, Andersen SH, Szyniarowski P, Corcelle-Termeau E, Valo E, Fehrenbacher N, Olsen CJ, Daugaard M, Egebjerg C, Bottzauw T, Kohonen P, Nylandsted J, Hautaniemi S, Moreira J, Jaattela M, et al. ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Mol Cell. 2012; 45:764-776.
67. Rao Malla R, Gopinath S, Alapati K, Gorantla B, Gondi CS, Rao JS. Knockdown of cathepsin B and uPAR inhibits CD151 and alpha3beta1 integrin-mediated cell adhesion and invasion in glioma. Mol Carcinog. 2013; 52:777-790.
68. Sivaparvathi M, Sawaya R, Wang SW, Rayford A, Yamamoto M, Liotta LA, Nicolson GL, Rao JS. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis. 1995; 13:49-56.
69. Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer. 2003; 3:489-501.
70. Steffan JJ, Snider JL, Skalli O, Welbourne T, Cardelli JA. Na+/H+ exchangers and RhoA regulate acidic extracellular pH-induced lysosome trafficking in prostate cancer cells. Traffic. 2009; 10:737-753.
71. Feng S, Cen J, Huang Y, Shen H, Yao L, Wang Y, Chen Z. Matrix metalloproteinase-2 and-9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins. PLoS One. 2011; 6:e20599.
72. Schubert-Unkmeir A, Konrad C, Slanina H, Czapek F, Hebling S, Frosch M. Neisseria meningitidis induces brain microvascular endothelial cell detachment from the matrix and cleavage of occludin: a role for MMP-8. PLoS Pathog. 2010; 6:e1000874.
73. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005; 75:5-14.
74. Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, Chaft JE, Kris MG, Huse JT, Brogi E, Massague J. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014; 156:1002-1016.
75. Gril B, Palmieri D, Qian Y, Anwar T, Liewehr DJ, Steinberg SM, Andreu Z, Masana D, Fernandez P, Steeg PS, Vidal-Vanaclocha F. Pazopanib inhibits the activation of PDGFRbeta-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells. Am J Pathol. 2013; 182:2368-2379.
76. Chuang HN, van Rossum D, Sieger D, Siam L, Klemm F, Bleckmann A, Bayerlova M, Farhat K, Scheffel J, Schulz M, Dehghani F, Stadelmann C, Hanisch UK, Binder C, Pukrop T. Carcinoma cells misuse the host tissue damage response to invade the brain. Glia. 2013; 61:1331-1346.
77. Bauer AT, Burgers HF, Rabie T, Marti HH. Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cereb Blood Flow Metab. 2010; 30:837-848.
78. Asahi M, Asahi K, Jung JC, del Zoppo GJ, Fini ME, Lo EH. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab. 2000; 20:1681-1689.
79. Seo JH, Guo S, Lok J, Navaratna D, Whalen MJ, Kim KW, Lo EH. Neurovascular matrix metalloproteinases and the blood-brain barrier. Curr Pharm Des. 2012; 18:3645-3648.
80. Sala G, Rapposelli IG, Ghasemi R, Piccolo E, Traini S, Capone E, Rossi C, Pelliccia A, Di Risio A, D'Egidio M, Tinari N, Muraro R, Iacobelli S. EV20, a Novel Anti-ErbB-3 Humanized Antibody, Promotes ErbB-3 Down-Regulation and Inhibits Tumor Growth In Vivo. Transl Oncol. 2013; 6:676-684.
81. Zhang Y, Akinmade D, Hamburger AW. Inhibition of heregulin mediated MCF-7 breast cancer cell growth by the ErbB3 binding protein EBP1. Cancer Lett. 2008; 265:298-306.
82. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3:1101-1108.
83. Momeny M, Malehmir M, Zakidizaji M, Ghasemi R, Ghadimi H, Shokrgozar MA, Emami AH, Nafissi S, Ghavamzadeh A, Ghaffari SH. Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa B-mediated induction of matrix metalloproteinase 9. Anticancer Drugs. 2010; 21:252-260.