Increased NID1 Expression among Breast Cancer Lung Metastatic Women; A Comparative Analysis between Naive and Treated Cases

Author(s): Tabinda Urooj*, Bushra Wasim, Shamim Mushtaq, Ghulam Haider, Syed N.N. Shah, Rubina Ghani, Muhammad F.H. Qureshi.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 15 , Issue 1 , 2020

Become EABM
Become Reviewer

Abstract:

Background: Lungs are the second most common reported site of distant metastasis in Breast cancer after bone. Mostly the studies were conducted in cell lines and animal model. To date, there is no blood biomarker reported that could determine the breast cancer progression in terms of lung metastasis.

Objective: The aim of this study is to determine Nidogen-1 (NID1)’s mRNA and protein expressions in non-invasive blood samples of breast cancer, in early (II) and lung metastasis advanced stages (III & IV) of naive and treated groups. To determine the functional association of NID1, we employed an in silico analysis, STRING database version 11.

Methods: A total of n = 175 cases of breast cancer were recruited in our study. Real time quantitative PCR and ELISA were performed to analyze the mRNA and protein expressions of NID1 respectively. An in silico method is also used to assess NID1’s interactome. Some significant patents related to this topic were also studied and discussed in this research paper.

Results: The results show high levels of NID1’s mRNA in the naive group (Group A) as compared to treated group (Group B). Similar trend of increased NID1’s protein expressions was also observed among naive and treated groups, respectively. Our results also show the significant impact of treatment on NID1’s gene and protein expressions. In silico analysis has revealed the functional association of NID1 with its different interactome protein partners.

Conclusion: The increased expression of NID1 in early to advanced naive as compared to the treated groups with lung metastasis makes it a promising marker which has pro-metastatic role in breast cancer.

Keywords: Basement membrane, blood biomarker, breast cancer, extracellular matrix, gene expression, lung metastasis, mRNA levels, Nidogen 1.

[1]
El Saghir NS, Khalil MK, Eid T, El Kinge AR, Charafeddine M, Geara F, et al. Trends in epidemiology and management of breast cancer in developing Arab countries: A literature and registry analysis. Int J Surg 2007; 5(4): 225-33.
[http://dx.doi.org/10.1016/j.ijsu.2006.06.015] [PMID: 17660128]
[2]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68(1): 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[3]
Wu Q, Li J, Zhu S, Wu J, Chen C, Liu Q, et al. Breast cancer subtypes predict the preferential site of distant metastases: A SEER based study. Oncotarget 2017; 8(17): 27990-6.
[http://dx.doi.org/10.18632/oncotarget.15856] [PMID: 28427196]
[4]
DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 2017; 67(6): 439-48.
[http://dx.doi.org/10.3322/caac.21412] [PMID: 28972651]
[5]
Ahmed A, Zahid I, Ladiwala ZFR, Sheikh R, Memon AS. Breast self-examination awareness and practices in young women in developing countries: A survey of female students in Karachi, Pakistan. J Educ Health Promot 2018; 7: 90.
[http://dx.doi.org/10.4103/jehp.jehp_147_17] [PMID: 30079361]
[6]
Sohail S, Alam SN. Breast cancer in pakistan-awareness and early detection 2007.
[7]
Khan F, Amatya B, Sayed TM, Butt AW, Jamil K, Iqbal W, et al. World Health Organisation Global Disability Action Plan 2014-2021: Challenges and perspectives for physical medicine and rehabilitation in Pakistan. J Rehabil Med 2017; 49(1): 10-21.
[http://dx.doi.org/10.2340/16501977-2149] [PMID: 28101563 ]
[8]
Taylor RBH. Composition for and method of preventing or treating breast cancer US6300367. (2001).
[9]
Kelly GE. Dietary supplements comprising soy hypocotyls containing at least one isoflavone US6497906. (2002).
[10]
Chang J, Clark GM, Allred DC, Mohsin S, Chamness G, Elledge RM. Survival of patients with metastatic breast carcinoma: Importance of prognostic markers of the primary tumor. Cancer 2003; 97(3): 545-53.
[http://dx.doi.org/10.1002/cncr.11083] [PMID: 12548595]
[11]
Kennecke H, Yerushalmi R, Woods R, Cheang M, Voduc D, Speers C, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol 2010; 28(20): 3271-7.
[http://dx.doi.org/10.1200/JCO.2009.25.9820] [PMID: 20498394]
[12]
Ambroggi M, Stroppa EM, Mordenti P, Biasini C, Zangrandi A, Michieletti E, et al. Metastatic breast cancer to the gastrointestinal tract: Report of five cases and review of the literature. Int J Breast Cancer 2012; 2012 439023
[http://dx.doi.org/10.1155/2012/439023] [PMID: 23091732]
[13]
Lyden D, Hoshino A, Matei I. Organtropic metastatic secretomes and exosomes in breast cancer. Joan and Sanford I Weill Medical College of Cornell University, New York, United States 2016.
[14]
Weigelt B, Peterse JL, van ’t Veer LJ. Breast cancer metastasis: Markers and models. Nat Rev Cancer 2005; 5(8): 591-602.
[http://dx.doi.org/10.1038/nrc1670] [PMID: 16056258]
[15]
Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: Challenges and treatment options. Drug Deliv Transl Res 2018; 8(5): 1483-507.
[http://dx.doi.org/10.1007/s13346-018-0551-3] [PMID: 29978332]
[16]
Bertozzi S, Londero AP, Cedolini C, Uzzau A, Seriau L, Bernardi S, et al. Prevalence, risk factors, and prognosis of peritoneal metastasis from breast cancer. Springerplus 2015; 4(1): 688.
[http://dx.doi.org/10.1186/s40064-015-1449-x] [PMID: 26576331]
[17]
Eckhardt BL, Francis PA, Parker BS, Anderson RL. Strategies for the discovery and development of therapies for metastatic breast cancer. Nat Rev Drug Discov 2012; 11(6): 479-97.
[http://dx.doi.org/10.1038/nrd2372] [PMID: 22653217]
[18]
Friedel G, Pastorino U, Ginsberg RJ, Goldstraw P, Johnston M, Pass H, et al. Results of lung metastasectomy from breast cancer: Prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases. Eur J Cardiothorac Surg 2002; 22(3): 335-44.
[http://dx.doi.org/10.1016/S1010-7940(02)00331-7] [PMID: 12204720]
[19]
Patanaphan V, Salazar OM, Risco R. Breast cancer: Metastatic patterns and their prognosis. South Med J 1988; 81(9): 1109-12.
[http://dx.doi.org/10.1097/00007611-198809000-00011] [PMID: 3420442]
[20]
Kaufmann JH. Genes differentially expressed in breast cancer US20130196314. (2013).
[21]
Ernst MF, van de Poll-Franse LV, Roukema JA, Coebergh JW, van Gestel CM, Vreugdenhil G, et al. Trends in the prognosis of patients with primary metastatic breast cancer diagnosed between 1975 and 2002. Breast 2007; 16(4): 344-51.
[http://dx.doi.org/10.1016/j.breast.2007.01.001] [PMID: 17303426]
[22]
McGuire A, Brown JA, Malone C, McLaughlin R, Kerin MJ. Effects of age on the detection and management of breast cancer. Cancers (Basel) 2015; 7(2): 908-29.
[http://dx.doi.org/10.3390/cancers7020815] [PMID: 26010605]
[23]
Esbah O, Turkoz FP, Turker I, Durnali A, Ekinci AS, Bal O, et al. Metaplastic breast carcinoma: Case series and review of the literature. Asian Pac J Cancer Prev 2012; 13(9): 4645-9.
[http://dx.doi.org/10.7314/APJCP.2012.13.9.4645] [PMID: 23167395]
[24]
Rayson D, Adjei AA, Suman VJ, Wold LE, Ingle JN. Metaplastic breast cancer: Prognosis and response to systemic therapy. Ann Oncol 1999; 10(4): 413-9.
[http://dx.doi.org/10.1023/A:1008329910362] [PMID: 10370783]
[25]
Samoon Z, Beg M, Idress R, Jabbar AA. Survival and treatment outcomes of metaplastic breast carcinoma: Single tertiary care center experience in Pakistan. Indian J Cancer 2019; 56(2): 124-9.
[http://dx.doi.org/10.4103/ijc.IJC_731_18] [PMID: 31062730]
[26]
Schlappack OK, Baur M, Steger G, Dittrich C, Moser K. The clinical course of lung metastases from breast cancer. Klin Wochenschr 1988; 66(17): 790-5.
[http://dx.doi.org/10.1007/BF01726581] [PMID: 3184763]
[27]
Dziadek M. Role of laminin-nidogen complexes in basement membrane formation during embryonic development. Experientia 1995; 51(9-10): 901-13.
[http://dx.doi.org/10.1007/BF01921740] [PMID: 7556571]
[28]
Li L, Zhang Y, Li N, Feng L, Yao H, Zhang R, et al. Nidogen-1: A candidate biomarker for ovarian serous cancer. Jpn J Clin Oncol 2015; 45(2): 176-82.
[http://dx.doi.org/10.1093/jjco/hyu187] [PMID: 25378651]
[29]
Raghu K. Basement membranes: Structure, assembly and role in tumor angiogenesis. Nat Med 2003; 3: 442-33.
[30]
Timpl R, Brown JC. Supramolecular assembly of basement membranes. BioEssays 1996; 18(2): 123-32.
[http://dx.doi.org/10.1002/bies.950180208] [PMID: 8851045]
[31]
Xian W. Isolation of non-embryonic stem cells and uses thereof US20190194608. (2019).
[32]
Halfter W, Oertle P, Monnier CA, Camenzind L, Reyes-Lua M, Hu H, et al. New concepts in basement membrane biology. FEBS J 2015; 282(23): 4466-79.
[http://dx.doi.org/10.1111/febs.13495] [PMID: 26299746]
[33]
Kefalides N, Alper R. Structure and organization of macromolecules in basement membranes Collagen. CRC Press: Boca Raton, FL, USA 2018; pp. 73-94.
[34]
Tsiper MV. Tumor encapsulation for prevention and treatment of metastatic cancer disease US8377484. (2013).
[35]
Hamilton GAW. Devices, systems and methods for inhibiting invasion and metastases of cancer US20170285003. (2017).
[36]
Bader BL, Smyth N, Nedbal S, Miosge N, Baranowsky A, Mokkapati S, et al. Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol Cell Biol 2005; 25(15): 6846-56.
[http://dx.doi.org/10.1128/MCB.25.15.6846-6856.2005] [PMID: 16024816]
[37]
Ekblom P, Ekblom M, Fecker L, Klein G, Zhang HY, Kadoya Y, et al. Role of mesenchymal nidogen for epithelial morphogenesis in vitro. Development 1994; 120(7): 2003-14.
[PMID: 7925005]
[38]
Pozzi A, Yurchenco PD, Iozzo RV. The nature and biology of basement membranes. Matrix Biol 2017; 57-58: 1-11.
[http://dx.doi.org/10.1016/j.matbio.2016.12.009] [PMID: 28040522]
[39]
Sanofi Aventis Germany GmbH Low molecular weight peptide derivatives as inhibitors of the laminin/nidogen interaction EP1070727. (2001).
[40]
Böse K, Nischt R, Page A, Bader BL, Paulsson M, Smyth N. Loss of nidogen-1 and -2 results in syndactyly and changes in limb development. J Biol Chem 2006; 281(51): 39620-9.
[http://dx.doi.org/10.1074/jbc.M607886200] [PMID: 17023412 ]
[41]
Dong L, Chen Y, Lewis M, Hsieh JC, Reing J, Chaillet JR, et al. Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Lab Invest 2002; 82(12): 1617-30.
[http://dx.doi.org/10.1097/01.LAB.0000042240.52093.0F] [PMID: 12480912]
[42]
Ulazzi L, Sabbioni S, Miotto E, Veronese A, Angusti A, Gafà R, et al. Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer. Mol Cancer 2007; 6(1): 17.
[http://dx.doi.org/10.1186/1476-4598-6-17] [PMID: 17328794 ]
[43]
Nan H, Xu M, Zhang J, Zhang M, Kraft P, Qureshi AA, et al. Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. Hum Mol Genet 2011; 20(13): 2673-9.
[http://dx.doi.org/10.1093/hmg/ddr154] [PMID: 21478494]
[44]
Pedrola N, Devis L, Llauradó M, Campoy I, Martinez-Garcia E, Garcia M, et al. Nidogen 1 and nuclear protein 1: Novel targets of ETV5 transcription factor involved in endometrial cancer invasion. Clin Exp Metastasis 2015; 32(5): 467-78.
[http://dx.doi.org/10.1007/s10585-015-9720-7] [PMID: 25924802]
[45]
Zhang Y, Xu B, Liu Y, Yao H, Lu N, Li B, et al. The ovarian cancer-derived secretory/releasing proteome: A repertoire of tumor markers. Proteomics 2012; 12(11): 1883-91.
[http://dx.doi.org/10.1002/pmic.201100654] [PMID: 22623176]
[46]
Willumsen NB. Nidogen-1 fragments assay US20190257837. (2019).
[47]
Chiang M-D, Kenneth W. Modulation of nidogen expression US20040097451 2004.
[48]
Alečković M, Wei Y, LeRoy G, Sidoli S, Liu DD, Garcia BA, et al. Identification of Nidogen 1 as a lung metastasis protein through secretome analysis. Genes Dev 2017; 31(14): 1439-55.
[http://dx.doi.org/10.1101/gad.301937.117] [PMID: 28827399]
[49]
Willumsen N, Bager CL, Leeming DJ, Bay-Jensen A-C, Karsdal MA. Nidogen-1 degraded by cathepsin s can be quantified in serum and is associated with non-small cell lung cancer. Neoplasia 2017; 19(4): 271-8.
[http://dx.doi.org/10.1016/j.neo.2017.01.008] [PMID: 28282545]
[50]
Lyden DCH. Methods and reagents for determination and treatment of organotropic metastasis US20190049435. (2019).
[51]
Hole SJWOR, Richard D. Methods of profiling gene expression, protein or metabolite levels US20040157229. (2004).
[52]
Crosara KTB, Moffa EB, Xiao Y, Siqueira WL. Merging in silico and in vitro salivary protein complex partners using the STRING database: A tutorial. J Proteomics 2018; 171: 87-94.
[http://dx.doi.org/10.1016/j.jprot.2017.08.002] [PMID: 28782718]
[53]
Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 2016; 45(D1): D362-8.
[PMID: 27924014]
[54]
Doudna JAJ. Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription US10421980. (2019).
[55]
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29(9): e45-5.
[http://dx.doi.org/10.1093/nar/29.9.e45] [PMID: 11328886]
[56]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[57]
Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 2012; 13(4): 227-32.
[http://dx.doi.org/10.1038/nrg3185] [PMID: 22411467]
[58]
Potti AN, Joseph R. Predicting responsiveness to cancer therapeutics US20100279957. (2010).
[59]
Benini S, Perbal B, Zambelli D, Colombo MP, Manara MC, Serra M, et al. In Ewing’s sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type. Oncogene 2005; 24(27): 4349-61.
[http://dx.doi.org/10.1038/sj.onc.1208620] [PMID: 15824736]
[60]
Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 2011; 17(7): 867-74.
[http://dx.doi.org/10.1038/nm.2379] [PMID: 21706029]
[61]
Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Müller S, et al. Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene 2011; 30(1): 54-64.
[http://dx.doi.org/10.1038/onc.2010.387] [PMID: 20818432]
[62]
Giancotti FG. Gene expression profiles associated with metastatic breast cancer US20150184247. (2015).
[63]
Minn AJ, Gupta GP, Siegel PM, et al. Genes that mediate breast cancer metastasis to lung 2005.Available from:. https://www.nature.com/articles/nature03799# supplementary-information
[http://dx.doi.org/10.1038/nature03799]
[64]
Vallacchi V, Daniotti M, Ratti F, Di Stasi D, Deho P, De Filippo A, et al. CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res 2008; 68(3): 715-23.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2103] [PMID: 18245471]
[65]
Bonnet SR. Method of in-vitro immunoassay US20130017537. (2013).
[66]
van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347(25): 1999-2009.
[http://dx.doi.org/10.1056/NEJMoa021967] [PMID: 12490681]
[67]
El-Helali AM. Gene signatures for cancer detection and treatment US20190127805. (2019).
[68]
Massague JZ. Gene Signatures for the prognosis of cancer US20110053804. (2011).
[69]
Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat 2010; 123(3): 725-31.
[http://dx.doi.org/10.1007/s10549-009-0674-9] [PMID: 20020197]
[70]
Krause AL. Cancer detection method US20090269744. (2009).
[71]
Massague JG, Gaorav P. Method of predicting and reducing risk of metastasis of breast cancer to lung US20080213258. (2008).
[72]
Lau TP, Roslani AC, Lian LH, Chai HC, Lee PC, Hilmi I, et al. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas. BMJ Open 2014; 4(8) e004930
[http://dx.doi.org/10.1136/bmjopen-2014-004930] [PMID: 25107436]
[73]
Piccolo SC. Prognosis of breast cancer patients by monitoring the expression of two genes US20150322533. (2015).
[74]
Dedhar S, Jewell K, Rojiani M, Gray V. The receptor for the basement membrane glycoprotein entactin is the integrin alpha 3/beta 1. J Biol Chem 1992; 267(26): 18908-14.
[PMID: 1527019]
[75]
Dong L-J, Hsieh J-C, Chung AE. Two distinct cell attachment sites in entactin are revealed by amino acid substitutions and deletion of the RGD sequence in the cysteine-rich epidermal growth factor repeat 2. J Biol Chem 1995; 270(26): 15838-43.
[http://dx.doi.org/10.1074/jbc.270.26.15838] [PMID: 7797588]
[76]
Yi X-Y, Wayner EA, Kim Y, Fish AJ. Adhesion of cultured human kidney mesangial cells to native entactin: Role of integrin receptors. Cell Adhes Commun 1998; 5(3): 237-48.
[http://dx.doi.org/10.3109/15419069809040294] [PMID: 9686320]
[77]
Khan R, Gupta N, Kumar R, Sharma M, Kumar L, Sharma A. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression. Clin Exp Metastasis 2014; 31(5): 585-93.
[http://dx.doi.org/10.1007/s10585-014-9652-7] [PMID: 24807734]
[78]
Hirakawa Y, Futaki S, Tanizaki H, Furukawa F, Maemura K, Kondo Y, et al. Enhanced expression of nidogen 1 around the nest of basal cell carcinoma compared with that around squamous cell carcinoma. Med Mol Morphol 2019; 52(2): 99-105.
[http://dx.doi.org/10.1007/s00795-018-0207-x] [PMID: 30276677]
[79]
Skog JKOB, Xandra O, Dennis B. Use of microvesicles in diagnosis and prognosis of medical diseases and conditions US20110003704. (2011).
[80]
Keely PJP, Paolo P. Stromal collagen in the diagnosis and characterization of breast cancer US7805183. (2010).
[81]
Di Vizio DF, Michael R. Methods for detecting and treating cancer metastasis US10254285. (2019).
[82]
Plasslick-Deetjen JB. Method and kit for diagnosing Epithelial-to- Mesenchymal Transition (EMT) of the peritoneum US20180246098. (2018).
[83]
Lawman MJPL. Materials and methods for treating oncological disease US7094603. (2006).
[84]
Lawman MJPL, Patricia D. Multi-indication mRNA cancer immunotherapy US9636388. (2017).
[85]
Lawman MJPL. Tumor cell vaccines US7795020. (2010).
[86]
Reinhardt CS. Treatment of metastatic breast cancer US20090304716. (2009).
[87]
Poola I. Methods for determining breast cancer risk US20190361027. (2019).


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 1
Year: 2020
Page: [59 - 69]
Pages: 11
DOI: 10.2174/1574892815666200302115438
Price: $65

Article Metrics

PDF: 11
HTML: 1