Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit tumor growth and metastasis in vivo

Department of Biochemistry, University of Oulu, Oulu, Finland.
International Journal of Cancer (Impact Factor: 5.09). 10/2009; 125(8):1814-25. DOI: 10.1002/ijc.24532
Source: PubMed


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.

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    • "mAb 8G9 may be the LMα5 antibody homologue of function-blocking mAbs BM165 and CM6 against the globular domain of the human and rat LMα3 chains, respectively [49], [50]. Recently, mAbs to the globular domain of the human LMα3 chain were shown to inhibit growth of human epithelial tumors grafted in mice [51], [52]. Likewise, antagonists of α5 laminins may inhibit tumor invasion and metastasis and have therapeutic potential in malignant diseases. "
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