Angiogenesis and tumour progression: migration-stimulating factor as a novel target for clinical intervention

A.M. Schor, S.L. Schor

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Migration-stimulating factor (MSF), a soluble genetically truncated isoform of fibronectin, is a potent oncofoetal regulatory molecule. Its 2.1-kb message is generated from the fibronectin gene by a variant of standard alternative splicing involving premature intra-intronic cleavage. MSF is constitutively expressed by both epithelial and stromal cells during foetal development and in patients with cancer, but is generally not expressed in healthy adults. MSF affects the behaviour of a broad range of potential target cells (fibroblasts, vascular, and epithelial) in terms of stimulation of their migration/invasion, matrix remodelling and induction of angiogenesis. It also functions as an autocrine survival factor for the angiogenic endothelium. MSF expression by foetal and cancer patient cells adherent to an appropriate matrix may be persistently switched off by a transient exposure to TGF-beta 1; conversely, MSF expression by adult dermal fibroblasts adherent to other matrices may be persistently switched on by a transient exposure to TGF-beta or various pharmacological agents known to alter gene expression by epigenetic mechanisms. The manifestation of MSF effects on target cells is similarly dependent on the inter-dependent signalling of soluble factors and matrix molecules. The significant association between elevated MSF expression and poor survival in patients with breast and oral cancer suggests that MSF may function as a driver of tumour progression. Accordingly, we suggest that the downregulation of MSF expression (eg, by siRNA or pharmacological agents) and/or inhibition of its bioactivities (by function-neutralising antibodies or MSF inhibitors) may provide a clinically efficacious means of improving treatment outcome in cancer patients.

Original languageEnglish
Pages (from-to)450-458
Number of pages9
JournalCurrent Eye Research
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • cancer
  • metastasis
  • MSF
  • angiogenesis
  • epigenetics
  • 5-azacytidine
  • CANCER-PATIENT FIBROBLASTS
  • HYALURONIC-ACID SYNTHESIS
  • MACULAR DEGENERATION
  • MESSENGER-RNA
  • FIBRONECTIN
  • CELLS
  • FETAL
  • EXPRESSION
  • INDUCTION
  • CARCINOMA

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