Laminin-511: a multi-functional adhesion protein regulating cell migration, tumor invasion and metastasis.
Laminins are major constituents of basement membranes. At least 16 isoforms have now been described, each with distinct spatio-temporal expression patterns and functions. The laminin-511 heterotrimer (α5β1γ1) is one of the more recent isoforms to be identified and a potent adhesive and pro-migratory substrate for a variety of normal and tumor cell lines in vitro. As our understanding of its precise function in normal tissues and in pathologies is rapidly unraveling, current evidence suggests an important regulatory role in cancer. This review describes published data on laminin-511 expression in several malignancies and experimental evidence from both in vitro and in vivo studies supporting its functional role during tumor progression. A particular emphasis is put on more recent studies from our laboratory and that of others indicating that laminin-511 contributes to tumor dissemination and metastasis in advanced breast carcinomas and other tumor types. Collectively, the experimental evidence suggests that high expression of laminin-511 has prognostic significance and that targeting tumor-laminin-511 interactions may have therapeutic potential in advanced cancer patients.
Metastasis Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. normand.pouliot@petermac.org
Normand
N
Pouliot
Nicole
N
Kusuma
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D039121:Integrin alpha6beta1 / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D039121:Integrin alpha6beta1; D007797:Laminin; D020033:Protein Isoforms; C551997:laminin-511, human