Fc. Bronfman et al., EXTRACELLULAR-MATRIX REGULATES THE AMOUNT OF THE BETA-AMYLOID PRECURSOR PROTEIN AND ITS AMYLOIDOGENIC FRAGMENTS, Journal of cellular physiology, 166(2), 1996, pp. 360-369
We have studied the influence of the extracellular matrix (ECM) on the
amount of beta-amyloid precursor protein (APP) and C-terminal amyloid
-bearing fragments in 3T3 fibroblasts. After incubation with ECM compo
nents, the cellular APP content of 3T3 cells changed. Besides, differe
nt substrata including collagen, fibronectin, laminin, vitronectin, an
d heparin, determined changes in the amount of a C-terminal 22 kDa-fra
gment. The regulation of amyloidogenic fragments by the ECM was transi
ent; in fact, when 3T3 cells were plated on tissue culture dishes coat
ed with collagen or vitronectin, maximal levels of the 22 kDa fragment
were observed 12 h after plating; in the presence of fibronectin, the
maximum level of the amyloidogenic fragment was obtained 36 h after p
lating. These results indicate that the ECM modulates in a transient w
ay the generation of APP-derived polypeptides containing the amyloid-b
eta-peptide (A beta). The ECM does not have a generalized effect on 3T
3 fibroblasts, because no significant differences in cell attachment,
growth rate, whole-cell polypeptide pattern, beta(1) integrin and a-tu
bulin levels were observed on cells grown on various matrix proteins.
Laminin, collagen, and heparin also influence the level of an amyloido
genic fragment of 35 kDa in Neuro 2A neuronal cells, without a signifi
cant change in the neuronal marker acetylcholinesterase. In this case,
however, a long-lasting response to ECM molecules was observed. These
observations provide evidence that ECM molecules influence APP biogen
esis, including the generation of amyloidogenic fragments containing t
he A beta peptide. Our studies might prove significant to understand t
he localized increment of beta-amyloid deposition in selected areas of
the brain of Alzheimer's patients. (C) 1996 Wiley-Liss, Inc.