A ROLE FOR PERLECAN IN THE SUPPRESSION OF GROWTH AND INVASION IN FIBROSARCOMA CELLS

Perlecan is a major heparan sulfate proteoglycan of basement membranes and cell surfaces. Because of its strategic location and ability to s tore and protect growth factors, perlecan has been implicated in the c ontrol of tumor cell growth and metastatic behavior. To test the role of perlecan in malignancy, we generated several stably transfected clo nes of HT-1080, a human fibrosarcoma cell line, harboring a perlecan c DNA in the antisense orientation. Surprisingly, clones with a reduced synthesis of perlecan mRNA and protein core grew faster, formed larger colonies in semisolid agar, and induced faster formation of s.c. tumo rs in nude mice than the wild-type cells, Their growth properties in v itro were independent of exogenous basic fibroblast growth factor, Red uction of perlecan expression was associated with three distinct prope rties typical of tumor cells with a more aggressive phenotype: enhance d migration through 8-mu m-pore filter, increased invasion in Matrigel -coated filters, and heightened adhesiveness to type IV collagen subst rata, These results thus provide the first evidence that perlecan may inhibit the growth and invasiveness of Fibrosarcoma cells in a basic f ibroblast growth factor-independent pathway and raise the possibility that perlecan may prevent the infiltration of host tissues in mesenchy mal neoplasms.