title: Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit tumor growth and metastasis in vivo.
abstract: Laminin-332 (LN-332), which is essential for epithelial cell adhesion and migration, is up-regulated in most invasive carcinomas. Association between LN-332 and carcinoma cell integrins and stroma collagen is thought to be important for tumor growth and metastasis. Here, we show that function blocking LN-332 antibodies interfering with cellular adhesion and migration in vitro evoke apoptotic pathways. The antibodies also target epithelial tumors in vivo. Antibodies against the cell binding domain of the alpha3 chain of LN-332 inhibited tumor growth by up to 68%, and antibodies against the matrix binding domains of the beta3 and gamma2 chains significantly decreased lung metastases. The LN-332 antibodies appear to induce tumor cell anoikis and subsequent programmed cell death and reduce migration by interfering with tumor cell matrix interactions.
authors: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors: Sirpa
authors: S
authors: Salo
authors: Ariel
authors: A
authors: Boutaud
authors: Anker Jon
authors: AJ
authors: Hansen
authors: Liqun
authors: L
authors: He
authors: Yi
authors: Y
authors: Sun
authors: Sylvia
authors: S
authors: Morales
authors: Amy
authors: A
authors: Venturini
authors: Paula
authors: P
authors: Martin
authors: Pasi
authors: P
authors: Nokelainen
authors: Christer
authors: C
authors: Betsholtz
authors: Ida Stenfeldt
authors: IS
authors: Mathiasen
authors: Karl
authors: K
authors: Tryggvason
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured; D000097794:Kalinin
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000097794:Kalinin