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Modulation of sarcoma cell movement and matrix interaction following manipulation of cell surface proteoglycans
Author(s) -
Rossi Silvia,
Lacrima Katia,
Garusi Elena,
Nicolosi Pier Andrea,
Affò Silvia,
Gulli Mariolina,
Gobbi Giuliana,
Vitale Marco,
Perris Roberto
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.480.9
Subject(s) - microbiology and biotechnology , metastasis , gene knockdown , biology , cell , sarcoma , cell adhesion , angiogenesis , cell migration , endocytic cycle , cancer research , cell culture , cancer , genetics , pathology , medicine , endocytosis
Cell surface proteoglycans are involved in several aspects of cancer biology including tumor progression, angiogenesis, and metastasis formation. Using soft‐tissue sarcoma as model we are trying to understand if different combinations of cell surface PGs can modulate tumour cell interaction with the host microenvironment and metastasis formation; so we are systematically modifying the constitutive patterns of these cells by in vitro gene transduction and RNAi knockdown of individual PGs in different sarcoma cell lines. Overexpression of GPC4, 5 and 6 shows a modulation of the other surface PGs and these new patterns of expression differentially affects the cell migratory and adhesive behaviour on purified ECM molecules and native matrices. RNAi‐mediated knockdown of some SDCs and GPC6 alters cell motility in vitro. Glypicans seem to undergo complex internalisation processes suggesting that endocytic pathways associated with these PGs may control the locomotory machinery. Both syndecans and glypicans seem to influence cell adhesion depending on the matrix substrate. Phospho‐proteomic screenings are in progress. Manipulated cells are assayed for their ability to form tumours and metastasis in mice. Our present findings are starting to delineate correlations between a given repertoire of surface PGs and malignant behavior of sarcoma.