Universität zu Köln

Chometon, Gretel, Cappuccini, Federica, Raducanu, Aurelia, Aumailley, Monique and Jendrossek, Verena ORCID: 0000-0003-1058-2107 (2014). The Membrane-targeted Alkylphosphocholine Erufosine Interferes with Survival Signals from the Extracellular Matrix. Anti-Cancer Agents Med. Chem., 14 (4). S. 578 - 592. SHARJAH: BENTHAM SCIENCE PUBL LTD. ISSN 1875-5992

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Abstract

Integrin-dependent adhesion of tumor cells to extracellular matrix proteins provides anchorage-dependent protection from cell death. In the present investigation we aimed to understand whether and how the paradigmatic membrane-targeted synthetic phospholipid analog erufosine is relevant for tumor cell adhesion to extracellular matrix proteins, cell survival and migration. The antineoplastic action of erufosine was analyzed with glioblastoma and prostate cancer cells adhering to fibronectin or collagen I using proliferation, adhesion and migration assays. The composition of adhesion contacts containing activated beta 1 integrins was studied using immunofluorescence. The importance of beta 1 integrins for the observed effects was analyzed in fibroblasts proficient or deficient in beta 1 integrin expression. Adhesion to collagen I and fibronectin increased the death threshold in serum-deprived tumor cells. Moreover, beta 1 integrin-deficient cells were more sensitive to erufosine-treatment compared to beta 1 integrin proficient cells suggesting a role of beta 1 integrins for matrix-mediated death resistance. Most importantly, erufosine disturbed the maturation of the cell adhesion complexes containing paxillin, activated beta 1 integrins and phosphorylated FAK, leading to a reduction of survival signals and inhibition of tumor cell adhesion and migration. These findings suggest that membrane-targeted synthetic phospholipids analogs may be of value for counteracting matrix-mediated treatment resistance in combined treatment approaches with radiotherapy or chemotherapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chometon, Gretel UNSPECIFIED UNSPECIFIED UNSPECIFIED Cappuccini, Federica UNSPECIFIED UNSPECIFIED UNSPECIFIED Raducanu, Aurelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Aumailley, Monique UNSPECIFIED UNSPECIFIED UNSPECIFIED Jendrossek, Verena UNSPECIFIED orcid.org/0000-0003-1058-2107 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-439508
DOI:	10.2174/1871520614666140313120417
Journal or Publication Title:	Anti-Cancer Agents Med. Chem.
Volume:	14
Number:	4
Page Range:	S. 578 - 592
Date:	2014
Publisher:	BENTHAM SCIENCE PUBL LTD
Place of Publication:	SHARJAH
ISSN:	1875-5992
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTEGRIN-MEDIATED ADHESION; LIPID RAFTS; ANTICANCER ALKYLPHOSPHOLIPIDS; DOWN-REGULATION; CELL-ADHESION; PI3K PATHWAY; TUMOR STROMA; CANCER; APOPTOSIS; COMBINATION Multiple languages Oncology; Chemistry, Medicinal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43950