Type IIB procollagen NH2-propeptide induces death of tumor cells via interaction with integrins αvβ3 and αvβ5

Abstract

Cartilage is resistant to tumor invasion. In the present study, we found that the NH2-propeptide of the cartilage-characteristic collagen, type IIB, PIIBNP, is capable of killing tumor cells. The NH2- propeptide is liberated into the extracellular matrix prior to deposition of the collagen fibrils. This peptide adheres to and kills cells from chondrosarcoma and cervical and breast cancer cell lines via the integrins α vβ5 and αvβ3. Adhesion is abrogated by blocking with anti αvβ 5 and αvβ3 antibodies. When αv is suppressed by small intefering RNA, adhesion and cell killing are blocked. Normal chondrocytes from developing cartilage do not express αvβ3 and αvβ 5 integrins and are thus protected from cell death. Morphological, DNA, and biochemical evidence indicates that the cell death is not by apoptosis but probably by necrosis. In an assay for invasion, PIIBNP reduced the number of cells crossing the membrane. In vivo, in a tumor model for breast cancer, PIIBNP was consistently able to reduce the size of the tumor. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.