Peptide analog of fibronectin that inhibits cell migration and ERK 1/2 activity

Szaniawska, B; Trembacz, H.; Miłoszewska, Joanna; Lipkowski, Andrzej W.; Misicka, Aleksandra; Ostrowski, Jerzy; Janík, P.

doi:10.1016/s0196-9781(01)00547-2

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…A stimulatory effect was found with the branched analog 4 containing fragments of fibronectin. Peptides 5–7 with sequences unrelated to fibronectin but containing residues of basic (Lys and/or Arg) and lipophylic alkyl (Leu) amino acid residues also stimulated cell migration, as did the dodeca peptide (8), which combines only lysine and leucine residues. Among the shorter, neutral peptides containing leucine and lacking lysine (9–12) only Boc‐Pro‐LeuOMe (10) significantly inhibited OVP 10 cells migration.…”

Section: Resultsmentioning

confidence: 98%

“…Recently, it has been demonstrated a modification of the primary sequence of this fragment yielded analogues with inhibitory properties on spontaneous and fibronectin‐stimulated cancer cell migration. Interestingly, these analogues themselves did not influence ERK 1/2 activity, but were able to decrease the stimulatory effects of native fibronectin (8). Such findings suggest a competitive interaction of peptide analogues with membrane fibronectin binding sites.…”

Section: Introductionmentioning

confidence: 99%

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A novel fibronectin‐related structural motif that modulates cell migration

Szaniawska

Kleczkowska

Trembacz

et al. 2005

The Journal of Peptide Research

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Fibronectins are extracellular proteins that play important roles in normal and pathological cell functions. These proteins exert concerted effects upon various active elements, of which probably only a fraction have been well characterized. Our previous studies suggested of existence of cell membrane binding sites that interact with fibronectin, modulate cell migration without influence on intracellular biochemistry. To search for element(s) responsible for recognition of these binding sites, we synthesized several model peptides and evaluated their influence on ovarian cancer OVP 10 cells migration, phosphorylation of ERK 1/2 and FAK expression. From our results we propose the existence of specific ‘leucine membrane binding site’ (LMBS). Inhibition of ovarian cancer cells migration by neutral leucine containing peptides is a result of formation of ligand‐membrane binding site complexes that in turn alter the physicochemical properties of the membrane, and/or competitively inhibit the binding of natural activators present in the extracellular fluid. Cationic peptides, containing basic arginine or lysine residues as well as lipophilic leucine, form complexes that change membrane charge and hydrophilicity, and activate migration. Lack of specific peptide sequence requirements suggests that a range of endogenous and exogenous molecules may competitively interact with the LMBS so as to modulate the physicochemical properties of cell membranes.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

A novel fibronectin‐related structural motif that modulates cell migration

Szaniawska

Kleczkowska

Trembacz

et al. 2005

The Journal of Peptide Research

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“…2. Integrins are crucial to cell invasion (Hood & Cheresh 2002), and inhibition of integrin b 3 function inhibits migration of human ovarian tumour cells (Szaniawska et al 2001). 3.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping for integrin b 3 Leu33Pro might be useful not only before ovarian cancer diagnosis, but also for prognostic purposes, perhaps in combination with measurement of its ligand osteopontin (Brakora et al 2004, Coppola et al 2004, Schorge et al 2004. Finally, in the future, genotyping at the time of diagnosis might also assist in drug selection: blockade of integrin b 3 -mediated signal transduction inhibits growth of human ovarian cancer cell lines (Szaniawska et al 2001, Cruet-Hennequart et al 2003, and interaction between integrin b 3 and its agonists and antagonists depends on Leu33Pro genotype (Michelson et al 2000, Boncler et al 2002, Wheeler et al 2002, Angiolillo et al 2004). …”

Section: Discussionmentioning

confidence: 99%

Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

Bojesen¹,

Kjær²,

Høgdall³

et al. 2005

Endocr Relat Cancer

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We previously demonstrated that integrin b 3 Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in casecontrol and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n=463+3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n=4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0-2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4-11) and 30 (10-92) per 10 000 person-years (log-rank P=0.02). The ageadjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1-13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin b 3 Leu33Pro homozygotes have an increased risk of ovarian cancer.

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