title: Host response to human breast Invasive Ductal Carcinoma (IDC) as observed by changes in the stromal proteome.
abstract: Following initial transformation, tumorigenesis, growth, invasion, and metastasis involves a complex interaction between the transformed tissue and the host, particularly in the microenvironment adjacent to the developing tumor. The tumor microenvironment itself is a unique outcome of the host reacting to the tumor and perhaps the tumor reacting to the host and in turn the tumor altering the host's response to give rise to an environment that ultimately promotes tumor progression. The tumor-adjacent stromal, sometimes referred to as "reactive stromal" or the desmoplastic stroma, has received some investigative studies, but it is incomplete, and likely different tumors promote a varied response and hence different reactive stroma. In this study, we have investigated the proteomics of the host response, both in vitro and in vivo, to breast epithelial cancer, in the former using tissue culture and in the latter laser microdissection of stromal tissue both adjacent and distal to breast invasive ductal cancer (IDC). From proteomic analysis of in vitro tissue culture studies, we observed that the stroma produced is related to the invasiveness of the stimulating breast cancer cell lines but different from that observed from the stromal proteome of archival tissue. In vivo we have identified several potential markers of a reactive stroma. Furthermore, we observed that the proteome of tumor-adjacent stroma differs from that of tumor-distal stroma. The proteomic description of human breast IDC stroma may serve to enhance our understanding of the role of stroma in the progression of cancer and may suggest potential mechanisms of therapeutic interdiction.
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine , Jordan Hall, Box 441, Charlottesville, Virginia 22908, United States.
authors.forename: Lavakumar A
authors.initials: LA
authors.lastname: Reddy
authors.forename: Leann
authors.initials: L
authors.lastname: Mikesh
authors.forename: Christopher
authors.initials: C
authors.lastname: Moskulak
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harvey
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sherman
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Jay W
authors.initials: JW
authors.lastname: Fox
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002853:Chromatography, Liquid; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017154:Stromal Cells / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D020543:Proteome
keywords: breast cancer; collagen XII; extracellular matrix; metastasis; periostin; stroma