Mini reviewProteoglycan control of cell movement during wound healing and cancer spreading
Section snippets
Alternative interpretations of the role of PGs in CNS repair
Spinal cord and brain lesion models are currently employed to understand the cellular and molecular mechanisms involved in the potential regeneration of the central nervous system. In experimentally induced tissue damages, axon regeneration appears to be strongly impeded by scarring at the site of injury, which is well documented to imply increased deposition of PGs carrying both CS and KS chains (reviewed by Silver and Miller, 2004). A plethora of studies have now clarified that up-regulation
Are PGs essential for the cell rearrangement occurring during wound healing?
Normal wound healing and tissue repair after acute damage are known to involve the formation of a granulation tissue and the elaboration of a provisional matrix highly enriched in PGs. Subsequent scarring at the site of injury, which is accompanied by different levels of fibrosis, also implies deposition of a PG-containing matrix provided by invading (myo)fibroblasts. Conversely, milder tissue damage, or chronic tissue degeneration, involves remodelling of the existing matrix and an augmented
Dual role of PG-M/versicans in wound healing phenomena
Together with tenascins, hyaluronan and interstitial collagens, PG-M/versicans are the primary matrix molecules to be up-regulated at sites of acute tissue damage and/or chronic tissue degeneration. Their involvement in tissue repair phenomena may entail a higher level of complexity since, in addition to the intricate metalloproteinase- and ADAMTS-dependent cleavage pattern of these PGs following injury (Somerville et al., 2003), there is a diverse regulation of the expression pattern of the
Surface bound and shedded PGs may influence tissue reconstitution by different mechanisms
In the best-studied wound-healing model, i.e. the skin, CD44 is known to play a major role in the fibroblast invasion of the damaged region (Henke et al., 1996). Accordingly, CD44 null mice exhibit partially perturbed wound-healing capacities, which may be reinforced by an abnormal recruitment of anti-inflammatory cells (Schmits et al., 1997). However, in contrast to what could be predicted, it is unlikely that the interaction of the CD44 with hyaluronan may be responsible for apparent
“PG size” makes the difference in the control of tumour invasion and metastatic spread
A characteristic trait of invasive solid tumours is the increased, or de novo induced, expression of several PGs. The majority of these macromolecules derive from a corresponding enhanced transcription in the neoplastic cells themselves, but a substantial contribution to the overall amount of PGs contained within a solid tumour lesion is also frequently afforded by its stromal component. Several investigations have documented that PG-M/versicans are primary constituents of this compartment of
PG-ligand regulatory loops and polarized PG surface distribution are critical for tumour cell motility and invasion
Over expression of CD44, and in particular the CD44v6 alternatively spliced variant, is conventionally believed to be detrimental for cancer patients because it may reflect the presence of more malignant metastatic tumours. Original studies indirectly suggested that CD44 could be implicated in melanoma cell motility and invasion in response to collagen type I substrates and following TGFβ stimulation of the cells (Faassen et al., 1993), and a similar suggestion was made with regard to glioma
Dual function of cell surface PGs in the conversion of transformed cells into motile phenotypes
One of the most classical experiments demonstrating the importance of cell surface PGs in tumour progression, and in particular the role of HS-carrying PGs, was originally performed by Jeffrey Esko and collaborators (Esko et al., 1988). This study highlighted that cells genetically engineered to be defective in the HS biosynthesis, and thereby harbouring a compositional deficit of their surface HSPGs, failed to form tumours both in vitro and in vivo. These findings were strongly corroborated by
Acknowledgments
Unpublished work of the authors' was supported by a number of national and international institutions. Primary financial contributions are currently provided by grants from the Italian Ministry of Health, the Italian Ministry of Education, University and Scientific Research (MIUR, projects FIRB 2001 and PRIN 2004), Associazione Italiana per la Ricerca sul Cancro (AIRC), and intramural research funds from the University of Parma. We are thankful to our numerous collaborators around the world for
References (153)
- et al.
Suppression of invasive behaviour of melanoma cells by stable expression of anti-sense perlecan cDNA
Ann. Oncol.
(1997) - et al.
Syndecan-1 expression is decreased with increasing aggressiveness of basal cell carcinoma
Am. J. Dermatopathol.
(2000) - et al.
Down-regulation of decorin, a transforming growth factor-beta modulator, is associated with scarless fetal wound healing
J. Pediatr. Surg.
(2001) - et al.
Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins
Blood
(2000) - et al.
CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration
J. Biol. Chem.
(2001) - et al.
A central segment of the NG2 proteoglycan is critical for the ability of glioma cells to bind and migrate toward type VI collagen
Exp. Cell Res.
(1997) - et al.
Distribution of PG-M/versican variants in human tissues and de novo expression of isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in vitro
J. Biol. Chem.
(2002) - et al.
Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterised dermatan sulfate-CD44 proteoglycan
J. Invest. Dermatol.
(2004) - et al.
Syndecan-2 expression in colorectal cancer-derived HT-29 M6 epithelial cells induces a migratory phenotype
Biochem. Biophys. Res. Commun.
(2001) - et al.
Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration
Dev. Biol.
(2001)