Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation.
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.
Petty
Aaron P
AP
School of Molecular Biosciences, Washington State University, Wegner Hall, Pullman, WA 99164-6534, USA.
Garman
Kiera L
KL
Winn
Virginia D
VD
Spidel
Celee M
CM
Lindsey
J Suzanne
JS
D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D018716:Molecular Mimicry / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*
C400567:LAMC2 protein, human; D007797:Laminin; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C482285:TOX4 protein, human