Title:Could Growth Factor-Mediated Extracellular Matrix Deposition and Degradation Offer the Ground for Directed Pharmacological Targeting in Fibrosarcoma?
Volume: 20
Issue: 23
Author(s): D. Nikitovic, A. Berdiaki, A. Banos, A. Tsatsakis, N. K. Karamanos and G. N. Tzanakakis
Affiliation:
Keywords:
Fibrosarcoma, extracellular matrix, growth factors, therapeutic targets, tumor cell signalling.
Abstract: The specific organization of the tumor extracellular matrix (ECM) is an intrinsic and basic step in the convoluted
pathways of tumorigenesis. Fibrosarcoma is a rare, lethal, malignant tumor originating from fibroblasts, characterized
by the formation of an abundant ECM. Fibroblastoid cells undergoing malignant transformation specifically alter
composition and organization of their ECM to facilitate growth, survival and invasion. Fibrosarcoma cells were shown to
have a high content and turnover of ECM components including hyaluronan, proteoglycans, collagens, fibronectin and
laminin. Cell signaling by endogenous growth factors, such as TGFβ, EGF, FGF2, VEGF and IFG-I, is directly correlated
to ECM remodeling, stroma formation and fibrosarcoma progression. In this regard, growth factors affect the expression
of matrix macromolecules, such as secreted and cell-associated proteoglycans, hyaluronan and its receptors CD44 and
RHAMM, as well as the expression and activity of matrix- degrading metalloproteinases, which are of critical importance
in tissue remodeling and fibrosarcoma progression. Therefore, therapeutic approaches considering growth factors and
their receptors as well as downstream signaling in human cancers may well be pharmacological targets being currently
explored. In this article, we focus on growth factor signaling regulating fibrosarcoma cell ECM organization at the level of
deposition and degradation of ECM macromolecules, the relation of ECM remodeling with fibrosarcoma cell malignant
behaviour as well as the putative strategies for its therapeutic intervention.
