Type IIB procollagen NH₂-propeptide induces death of tumor cells via interaction with integrins α_vβ₃ and α_vβ₅

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 α_vβ₃. Adhesion is abrogated by blocking with anti α_vβ ₅ and α_vβ₃ antibodies. When α_v is suppressed by small intefering RNA, adhesion and cell killing are blocked. Normal chondrocytes from developing cartilage do not express α_vβ₃ and α_vβ 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.