The biology of perlecan: themultifaceted heparansulfateproteoglycan of basement membranes andpericel lular matrices
- R. V. lozzo, I. R. Cohen, S. Grissel, A. D. Murdoch
- Biochem. J.,
(7). In addition, tumor cytokines that influence the turnover and biosynthesis of proteoglycans in host cells are known to bind perlecan and can act as a reservoir of growth factors to stimulate tumor growth and angiogenesis (3). In this report, we have investigated perlecan expression in invasive melanomas and found that the perlecan mRNA steady-state levels were elevated up to 15-fold. This increase correlated with abundant deposition of perlecan proteoglycan in the pericellular matrix of the tumor cells. Using the human melanoma cell line MeWo and its more actively metastatic variant 70W, we were able to establish a correla tion between perlecan up-regulation and invasiveness of the tumor cells. The 70W subline is able to form brain colonies in nude mice (8, 9) and exhibits an increased ability to invade the reconstituted base ment membrane Matrigel following NT treatment (10). Here we report that the expression of perlecan protein core is up-regulated in the 70W cells on stimulation with two different NTs, NGF and NT-3. The transcript levels were up-regulated within 10 min of NT treat ment, indicating that perlecan is an early response gene in this system. Secretion of the perlecan protein core appeared within 30 mm, there fore preceding the secretion of heparanase. These results indicate that perlecan may play a major role in the initial stages of invasion and during the progressive pathways of human melanoma into the inva sive phenotype.