Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit tumor growth and metastasis in vivo.
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.
Salo
Sirpa
S
Department of Biochemistry, University of Oulu, Oulu, Finland.
Boutaud
Ariel
A
Hansen
Anker Jon
AJ
He
Liqun
L
Sun
Yi
Y
Morales
Sylvia
S
Venturini
Amy
A
Martin
Paula
P
Nokelainen
Pasi
P
Betsholtz
Christer
C
Mathiasen
Ida Stenfeldt
IS
Tryggvason
Karl
K
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
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000097794:Kalinin