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Antibodies blocking adhesion and matrix binding domains of laminin‐332 inhibit tumor growth and metastasis in vivo
Author(s) -
Salo Sirpa,
Boutaud Ariel,
Hansen Anker Jon,
He Liqun,
Sun Yi,
Morales Sylvia,
Venturini Amy,
Martin Paula,
Nokelainen Pasi,
Betsholtz Christer,
Mathiasen Ida Stenfeldt,
Tryggvason Karl
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24532
Subject(s) - anoikis , laminin , integrin , blocking antibody , cancer research , metastasis , antibody , in vivo , microbiology and biotechnology , cell adhesion , cell migration , fibronectin , biology , extracellular matrix , cell adhesion molecule , chemistry , cell , cancer , immunology , biochemistry , genetics
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 α3 chain of LN‐332 inhibited tumor growth by up to 68%, and antibodies against the matrix binding domains of the β3 and γ2 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. © 2009 UICC