Document Detail

Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation.
MedLine Citation:
PMID:  17456780     Owner:  NLM     Status:  MEDLINE    
Molecular requirements for carcinoma cell interactions with the microenvironment are critical for disease progression but are poorly understood. Integrin alpha v beta 5, which senses the extracellular matrix, is important for carcinoma cell dissemination in vivo. alpha v beta 5 signaling induces Mig-7, a novel human gene product that is apparently carcinoma-specific. We hypothesized that Mig-7 expression facilitates tumor cell dissemination by increasing invasion and vasculogenic mimicry. Results show that embryonic cytotrophoblasts up-regulated Mig-7 expression before they acquired an invasive phenotype capable of pseudovasculogenesis. Mig-7 protein primarily co-localized with vasculogenic mimicry markers factor VIII-associated antigen, vascular endothelial-cadherin, and laminin 5 gamma 2 chain domain III fragment in lymph node metastases. Overexpression of Mig-7 increased gamma 2 chain domain III fragments known to contain epidermal growth factor (EGF)-like repeats that can activate EGF receptor. Interestingly, EGF also induced Mig-7 expression. Carcinoma cell adhesion to laminins was significantly reduced by Mig-7 expression. Remarkably, in two-dimensional and three-dimensional Matrigel cultures, Mig-7 expression caused invasion and vessel-like structures. Melanoma cells, which were previously characterized to invade aggressively and to undergo vasculogenic mimicry, expressed Mig-7. Taken together, these data suggest that Mig-7 expression allows cells to sense their environment, to invade, and to form vessel-like structures through a novel relationship with laminin 5 gamma 2 chain domain III fragments.
Aaron P Petty; Kiera L Garman; Virginia D Winn; Celee M Spidel; J Suzanne Lindsey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  170     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-06-26     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1763-80     Citation Subset:  AIM; IM    
School of Molecular Biosciences, Washington State University, Wegner Hall, Pullman, WA 99164-6534, USA.
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MeSH Terms
Blotting, Western
Carcinoma / blood supply,  metabolism*,  pathology
Cell Adhesion
Cells, Cultured
Disease Progression
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Laminin / metabolism
Mice, Nude
Molecular Mimicry / physiology
Neoplasm Invasiveness*
Neoplasm Proteins / biosynthesis*
Neovascularization, Pathologic / metabolism*
Placenta / metabolism
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Trophoblasts / metabolism*
Grant Support
Reg. No./Substance:
0/LAMC2 protein, human; 0/Laminin; 0/Mig-7 protein, human; 0/Neoplasm Proteins; 0/RNA, Small Interfering
Comment In:
Am J Pathol. 2007 May;170(5):1454-6   [PMID:  17456752 ]

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