A POSSIBLE ROLE OF 92 KDA TYPE-IV COLLAGENASE IN THE EXTRAMEDULLARY TUMOR-FORMATION IN LEUKEMIA

Production of metalloproteinases such as collagenases has been reporte d to be involved in the metastasis of cancer cells. Granulocytic sarco ma in extramedullary sites can be formed by similar steps to other can cers. In this study, we have examined the secretion of type IV collage nases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in severa l human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in der mal tissues. We have also examined the invasive capacity of these leuk emia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell li nes used in this study, only the granulocytic sarcoma cell line was fo und to secrete type IV collagenase constitutively. Other myeloid leuke mia cell lines such as HL-60 and U-937 produced type IV collagenase on ly after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metallo proteinases. In vitro invasion assay revealed that the granulocytic sa rcoma cell line showed higher invasive capacity than the other cell li nes. These results suggest that the secretion of 92 kDa type IV collag enase plays a role in the leukemia cells' invasion of extramedullary t issues.