Journal of Cell Science o:10.1242/jcs.121590 doi: 4108–4120 126, ß Science Cell of Journal 2013 June 3 Accepted uoa O805 USA 80045, CO Aurora, USA 94143, CA Francisco, San USA 80045, CO Aurora, USA rgntreihla el hthv eue ucpiiiyto susceptibility reduced differentiated One of have population 1988). that distinct al., cells a et epithelial to progenitor (Sinha rise that rodents gives is protection parous pregnancy confers pregnancy full-term to how for similar explanation 1988). very estrogen al., rodents et nulliparous is of Sinha of 2005; morphology pregnancy-levels al., epithelial mammary et However, to Russo 1999; exposure Smith, and (Medina after following or administrated are is pregnancy carcinogens early-age incidence when tumor rodents with in observations, associated reduced epidemiologic these risk In pregnancy’. of of in effect support ‘protective Schonfeld reduction the breast termed 2007; full-term been The developing al., has pregnancy 2011). et of first Reinier al., risk 1970; et early-age al., lifetime et woman’s (MacMahon between cancer a relationship and pregnancy inverse is cancer the breast human of characteristic epidemiological striking A Introduction with data consistent our manner Furthermore, a phenotype. in invasive collagen, words: the fibrillar Key particularly to genes ECM, contributor mammary of key of a upregulation organization is and cells, alone, suppression. composition tumor density the tumor alters than in parity-induced These parity rather genes. E-cadherin that in organization, metalloproteinase-encoding show junctional and collagen less stiffness mesenchymal-specific in that of is and show downregulation increases rats and data organization including junctions, parous cell–cell attributes, collagen of with of of consistent distribution components tumor-suppressive phenotypes subcellular glands implicating encoding cellular the induces mammary induces alters stiffness, I and I the collagen cells stromal (fibrillar) tumor collagen in linearized mammary in that in observed demonstrate behavior to collagen decrease we invasive generation models, an abundant indolent culture a Second-harmonic of cell nulliparous the unexpected. from 3D tissue with using Using that were breast protection. transitioning associated observed to results revealed extended these that of and microscopy observation collagen, with an capable force fibrillar linearized matrix, compared of atomic parous cells invasion decreases attributes in and tumor I matrix) pro-tumorigenic cell imaging collagen (parous the tumor Utilizing of rats Given abundance with protection. parous women. increased associated from Here, parous an this (ECM) epithelium. phenotypes identifies mammary matrix analysis in cellular the Proteomic extracellular stroma impedes in matrix. mammary changes and that mammary by demonstrate growth part the we in tumor states, mediated of invasive is role or pregnancy early-age proliferative the to attributed address risk we cancer breast in reduction The Summary ( correspondence for *Author 7 6 5 4 3 2 1 Maller Ori cancer breast from protection pregnancy-induced in architecture Collagen 4108 i-ho Tan Aik-Choon nvriyo ooaoCne etr lg50 ut 04,101E1t lc,Arr,C 04,USA 80045, CO Aurora, Place, Avenue, 17th 17th E E 13001 12801 6004C, Campus, Suite Medical 500, Anschutz Bldg USA Colorado 94720, Center, CA of Cancer Berkeley, University Colorado 478, Medicine, of Hall of University Stanley Ave, School California, Parnassus Biology, Berkeley 513 California–Berkeley, Developmental Francisco, of and San University Cell California, Center, of Oncology Ave, of Department – 17th University Sciences E Regeneration, Physical 12801 Tissue Area Campus, and Bay Medical Bioengineering Anschutz for 80045, Colorado Center CO of and Aurora, University Surgery Avenue, Medicine, of 17th of Department E School 12801 Genetics, 5117, Molecular USA RC-1S, 80045, and MS8104, CO Biochemistry Campus, Aurora, of Avenue, Medical 17th Department Anschutz E Colorado 12801 Campus, of Medical University Anschutz Colorado Biology, of Cancer University in Medicine, of Program School Oncology, Medical of Division 03 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2013. -ahrn olgnognzto,Itgi inln,Tmrsprsieetaellrmti,ECM matrix, extracellular Tumor-suppressive signaling, Integrin organization, Collagen E-cadherin, 1,2 ikC Hansen C. 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Ansorge, efre h rtoi nlssaditrrtdrltddata; K.C.H. related writer; manuscript interpreted with assisted manuscript and and studies primary tumor analysis mouse performed proteomic was T.R.L. the and performed experiments, data all in partook interpreted or performed experiments, designed O.M. manuscript. contributions the Author into input critical and for Gutierrez-Hartmann AMC) Arthur (UC thank Jedlicka also Paul We inhibitor. U0126 the laa,J,Bsei . rbls,M,Tea,X,Fby . Farre B., Fabry, X., Trepat, M., Grabulosa, L., Buscemi, J., Alcaraz, and F. Talamantes, G., Thordarson, M., S. Swanson, C., R. Guzman, J., T. Abrams, References at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.121590/-/DC1 online available release material number for Supplementary PMC [grant in award Deposited P.S.). Komen memory months. in (to 12 G Fund, Schedin after Charitable Kazda Susan Dobbs Connie the a of and and I.A.]; to T.R.L.] Division also PDF12230246 England to was PF-08-257-01- New number work CSM [grant Society Odyssey Cancer The Spin Fellowship R21 American Facility]. Postdoctoral an V.M.W., Spectrometry to by CA046934 and Mass supported P30 Facility, Proteomic Z.W. Spectrometry Microscopy the Mass Light to Advanced Proteomic to ES019458 and RR025780 Core UL1 U01 of K.H.; CA138818- to Institutes V.M.W., R01 CA132741 National numbers to the [grant US from Institute) 01A1 the received Cancer from was (National Award work Health Idea this Additional P.S.]. for an to BC095850 support by number [grant supported Defense of mainly Department was work This Funding co-wrote and and data sub- microarray interpreted analysis manuscript. integrin experiments, transcriptome the evaluating designed AFM interpreted P.S. in A.C.T. analysis; performed assisted distribution; R.P. 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