Glycerophosphoinositols inhibit the ability of tumour cells to invade the extracellular matrix.
The naturally occurring phosphoinositide metabolite, glycerophosphoinositol 4-phosphate, has recently been shown to induce rearrangements in the actin cytoskeleton through modulation of the small GTPases, Rac and Rho. Since this is directly linked to cell spreading and remodelling, we have evaluated the potential role of glycerophosphoinositol 4-phosphate and related metabolites in tumour cell invasion. The biological effects of these compounds were tested in a number of cellular activities related to cell spreading, including cell migration and cell invasion. We find that unlike other inositol-containing molecules, such as the inositol phosphates, glycerophosphoinositol and glycerophosphoinositol 4-phosphate prevent the invasion of epithelium-derived MDA-MB-231 breast carcinoma and A375MM melanoma cell lines through the extracellular matrix; this is due to a decreased ability to degrade matrix components. These data identify a specific activity of the glycerophosphoinositols that can be exploited for their development as novel anti-invasive drugs.
Buccione
Roberto
R
Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro (Chieti), Italy.
Baldassarre
Massimiliano
M
Trapani
Valentina
V
Catalano
Carmen
C
Pompeo
Arsenio
A
Brancaccio
Anna
A
Giavazzi
Raffaella
R
Luini
Alberto
A
Corda
Daniela
D
D000199:Actins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002633:Chemotaxis / Q000187:drug effects; D003599:Cytoskeleton / Q000737:chemistry; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008545:Melanoma / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control
D000199:Actins; D000970:Antineoplastic Agents; D007295:Inositol Phosphates; C062528:glycero-3-phosphoinositol 4-phosphate; D020782:Matrix Metalloproteinases