ANOXIA, WOUND-HEALING, VL30 ELEMENTS, AND THE MOLECULAR-BASIS OF MALIGNANT CONVERSION

Although VL30 retrotransposable elements have been associated with cer tain cancers for nearly twenty years, because of their expression in r odent malignancies and recombination into murine sarcoma viruses, thei r causative role, if any, in cancer has been uncertain and enigmatic. Recent findings suggest loss of normal transcriptional control of spec ific VL30 element expression may make a critical contribution to tumor progression at a step associated with malignant conversion, by bringi ng into play a cellular program normally involved in wound healing. Th is program, the fibroblast anoxic response system, includes an adaptat ion to glycolytic metabolism, secretion of metalloproteinases, and act ivation of an endonuclease. While appropriate for facilitating debris removal during wound healing, loss of control of this program in a cel l which has already progressed to the benign neoplastic state has the potential to simultaneously produce the invasiveness and genomic insta bility characteristic of malignancy. Examination of tumors and tumor d erived cell lines has confirmed that key aspects of this system are in fact activated in cancer.