title: Annexin A1 in primary tumors promotes melanoma dissemination.
abstract: Metastatic melanoma is one of the most aggressive forms of skin cancer and has a poor prognosis. We have previously identified Annexin A1 (ANXA1) as a potential murine melanoma-spreading factor that may modulate cell invasion by binding to formyl peptide receptors (FPRs). Here, we report that (1) in a B16Bl6 spontaneous metastasis model, a siRNA-induced decrease in tumoral ANXA1 expression significantly reduced tumoral MMP2 activity and number of lung metastases; (2) in a retrospective study of 61 patients, metastasis-free survival was inversely related to ANXA1 expression levels in primary tumors (HR 3.15 [1.03-9.69], p = 0.045); (3) in human melanoma cell lines, ANXA1 level was positively correlated with in vitro invasion capacity whereas normal melanocytes contained low ANXA1 levels, and (4) the ANXA1 N-terminal peptide ANXA12-26 stimulated MMP2 activity after interaction with FPRs and significantly stimulated the in vitro invasion of melanomas by acting on FPRs. These findings identify ANXA1 as a proinvasive protein in melanoma that holds promise as a potential prognostic marker and therapeutic target.
authors.affiliation: Clermont-Ferrand Université, Université d'Auvergne, INSERM U990, Imagerie Moléculaire et Thérapie Vectorisée, BP 184, 63000, Clermont-Ferrand, France.
authors.forename: Zied
authors.initials: Z
authors.lastname: Boudhraa
authors.forename: Fabien
authors.initials: F
authors.lastname: Rondepierre
authors.forename: Lemlih
authors.initials: L
authors.lastname: Ouchchane
authors.forename: Roselyne
authors.initials: R
authors.lastname: Kintossou
authors.forename: Anna
authors.initials: A
authors.lastname: Trzeciakiewicz
authors.forename: Frederic
authors.initials: F
authors.lastname: Franck
authors.forename: Jean
authors.initials: J
authors.lastname: Kanitakis
authors.forename: Bruno
authors.initials: B
authors.lastname: Labeille
authors.forename: Juliette
authors.initials: J
authors.lastname: Joubert-Zakeyh
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bouchon
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Perrot
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mansard
authors.forename: Janine
authors.initials: J
authors.lastname: Papon
authors.forename: Pierre
authors.initials: P
authors.lastname: Dechelotte
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: Mathilde
authors.initials: M
authors.lastname: Bonnet
authors.forename: Michel
authors.initials: M
authors.lastname: D'Incan
authors.forename: Françoise
authors.initials: F
authors.lastname: Degoul
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017305:Annexin A1 / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D017305:Annexin A1; D017931:DNA Primers