title: Interplay between cadherins and α2β1 integrin differentially regulates melanoma cell invasion.
abstract: BACKGROUND
  Malignant transformation of melanocytes frequently coincides with an alteration in the expression of cell-cell adhesion molecules (cadherins) and cell-extracellular matrix proteins (integrins). How these two adhesion systems interplay to impact on cell invasion remains to be described in melanoma.
  
  
  METHODS
  Cell adhesion networks were localised by immunofluorescence in human primary cutaneous melanoma, metastatic melanoma in the lymph nodes, and melanoma cell lines. The role of these cell adhesion networks was assessed both in vivo, by analysing their impact on tumour growth in mice, and in vitro, with the use of functional tests including cell aggregation and cell migration.
  
  
  RESULTS
  We found that α2β1 integrin associates with both E-cadherin and N-cadherin to form two adhesive networks, distinguishable by the interaction-or not-of α2β1 integrin with type I collagen. N-cadherin/α2β1 integrin and E-cadherin/α2β1 integrin networks differently participated towards tumour growth in mice. The N-cadherin/α2β1 integrin network showed specific involvement in melanoma cell invasion and migration towards type I collagen. On the other hand, the E-cadherin/α2β1 network regulated cell-cell adhesion.
  
  
  CONCLUSIONS
  This suggests that different signalling environments can be generated, depending on the type and/or local concentration of cadherin present in the adhesion complex, which potentially leads to differential cell responses. Further clarification of how these adhesive networks are regulated is fundamental to understanding important physiological and pathological processes such as morphogenesis, wound healing, tumour invasion and metastasis.
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Siret
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Terciolo
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Dobric
authors.affiliation: APHM, Marseille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Habib
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Germain
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Renaté
authors.initials: R
authors.lastname: Bonnier
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lombardo
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Rigot
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: André
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D015820:Cadherins; D038982:Integrin alpha2beta1