Type IIB procollagen NH(2)-propeptide induces death of tumor cells via interaction with integrins alpha(V)beta(3) and alpha(V)beta(5).
Cartilage is resistant to tumor invasion. In the present study, we found that the NH(2)-propeptide of the cartilage-characteristic collagen, type IIB, PIIBNP, is capable of killing tumor cells. The NH(2)-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 alpha(v)beta(5) and alpha(v)beta(3). Adhesion is abrogated by blocking with anti alpha(v)beta(5) and alpha(v)beta(3) antibodies. When alpha(v) is suppressed by small intefering RNA, adhesion and cell killing are blocked. Normal chondrocytes from developing cartilage do not express alpha(v)beta(3) and alpha(v)beta(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.
Wang
Zhepeng
Z
Department of Orthopedic Surgery, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, MI 63110, USA.
Bryan
Jennifer
J
Franz
Carl
C
Havlioglu
Necat
N
Sandell
Linda J
LJ
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism*; D002448:Cell Adhesion; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D004275:DNA, Ribosomal / Q000235:genetics; D004622:Embryo, Mammalian / Q000502:physiology; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D004275:DNA, Ribosomal; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments; D011347:Procollagen; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D012313:RNA