Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation

Am J Pathol. 2007 May;170(5):1763-80. doi: 10.2353/ajpath.2007.060969.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma / blood supply
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Adhesion
  • Cells, Cultured
  • Disease Progression
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Laminin / metabolism
  • Mice
  • Mice, Nude
  • Molecular Mimicry / physiology
  • Neoplasm Invasiveness*
  • Neoplasm Proteins / biosynthesis*
  • Neovascularization, Pathologic / metabolism*
  • Placenta / metabolism
  • Pregnancy
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trophoblasts / metabolism*

Substances

  • LAMC2 protein, human
  • Laminin
  • Mig-7 protein, human
  • Neoplasm Proteins
  • RNA, Small Interfering