Correlation between 99mTc-(V)-DMSA uptake and constitutive level of phosphorylated focal adhesion kinase in an in vitro model of cancer cell lines.
OBJECTIVE
Although a number of prognostic indicators have been developed, it is still difficult to predict the biological behaviour of all cancer types.( 99m)Tc-(V)-DMSA (V DMSA) uptake and focal adhesion kinase (FAK) expression and activation level could be potential agents for this purpose. We hypothesised the existence of a correlation between V DMSA, whose uptake is linked to phosphate ions, essential compounds for tumour growth and cell proliferation, and the adhesion protein FAK, whose elevated expression and level of constitutive activation are implicated in cancer progression. The aim of this study was to assess the relationship between V DMSA incorporation rate and FAK expression and activation by phosphorylation on tyrosine 397 residue.


METHODS
We determined V DMSA uptake in six different cancer cell lines and we measured FAK expression and activation by using Western Blotting analysis. Correlations with factors known to be associated with poor prognosis, such as invasive potential, resistance to chemotherapy and proliferation rate, were also investigated.


RESULTS
The cell lines exhibited different V DMSA incorporation rates. In addition, these cells showed the same FAK expression, but various degrees of activation. A correlation was observed between V DMSA uptake and level of FAK phosphorylation and between V DMSA or constitutive FAK activation and proliferation rate. However, no correlation was shown between these parameters and the other factors tested, i.e. invasive potential and anticancer drug resistance.


CONCLUSIONS
The results of this in vitro study clearly demonstrate that phosphorylation of FAK, proliferation rate and V DMSA uptake are closely related. Because proliferation and a high level of constitutive FAK activation are linked to cancer progression, it can be assumed that in vivo V DMSA uptake reflects tumour aggressiveness.
Denoyer
Delphine
D
Department of Biophysics and Radiopharmaceuticals, Cell Survival and Adhesion Research Group, Jacques Lisfranc Faculty of Medicine, University of Saint-Etienne, 5 rue Ambroise Paré, 42023, Saint-Etienne, France. delphine.denoyer@univ-st-etienne.fr
Perek
Nathalie
N
Le Jeune
Nathalie
N
Cornillon
Jérôme
J
Dubois
Francis
F
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000473:pathology*; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007477:Ions; D007700:Kinetics; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry
D000970:Antineoplastic Agents; D007477:Ions; D010710:Phosphates; D019275:Radiopharmaceuticals; D014443:Tyrosine; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases