title: Laminin-332-rich tumor microenvironment for tumor invasion in the interface zone of breast cancer.
abstract: Dense fibrosis, which is caused by desmoplastic reaction, is usually found in invasive ductal carcinoma and may represent the alteration of the tumor microenvironment preceding tumor invasion. Thus, the dense fibrotic zone around invasive ductal carcinoma can be considered to be the actual tissue site of tumor microenvironment, where the precedent alterations for tumor invasion occur. To characterize the dense fibrotic zone, we classified invasive ductal carcinoma tissue into a tumor zone, a normal zone, and the novel interface zone (IZ), which shows dense fibrosis. The postulated IZ is a 5-mm-wide belt that circles the tumor margin and overlaps with normal tissue. Of the extracellular matrix components, laminin-332 was specifically overexpressed in the IZ. Events that appear to be similar to the epithelial-mesenchymal transition, a novel source of myofibroblast formation from epithelial cells, were observed in the IZ, according to the following characteristics: overexpression of matrix metalloproteinase 3, membrane type 1-matrix metalloproteinase, snail, and zinc finger E-box-binding homeobox 1, and the gain of N-cadherin expression, as well as the down-regulation of miR200c. The myofibroblasts isolated from the IZ, which were designated interface zone-fibroblast, displayed laminin-332 and membrane type 1-matrix metalloproteinase overexpression, in contrast with both cancer-associated fibroblasts and normal breast fibroblasts. Taken together, our results suggest that the IZ, which shows dense fibrosis, may provide a specialized microenvironment for guiding tumor invasion: the fibrosis caused by laminin-332 overexpressing myofibroblast formation (interface zone-fibroblast) via epithelial-mesenchymal transition.
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: An
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Gao
authors.forename: Haengran
authors.initials: H
authors.lastname: Park
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D039161:Integrin alpha6beta4 / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D059016:Tumor Microenvironment; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000097794:Kalinin
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; D039161:Integrin alpha6beta4; D053511:Matrix Metalloproteinase 14; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000097794:Kalinin; C533896:MIRN200 microRNA, human; C486307:ZEB1 protein, human