Titration of IRAP protein

Introduction

Many different forms of cancer affect over 25 million people in the world and are the cause of death for around 7 million each year. Breast cancer is the most frequent representing 13.5 of all cancers.

An identification of the extent to which cancers are chemoresistant (including breast, ovary, and endometrial cancers) using diagnostic tools, would enable a better  identification of high risk patients and help develop treatments that are better suited to these specific illnesses.

The malignancy and chemo resistance of cancerous cells are directly correlated to the expression of the glucose transporter GLUT4 which proves to be extremely useful as a diagnostic marker for certain cancers.

Services and Product Offerings

Our offering centres on a diagnostic method based on the titration of  the IRAP protein (insulin-regulated AminoPeptidase), a transmembrane protein which colocolises with the glucose trnasporter GLUT4.

It has been proved that the expression of IRAP is directly correlated to that of GLUT4 and that it increases according to the level of cancer (endometrial and breast cancers).

At the moment it is inserted in the plasmic membrane the extracellular domain of IRAP (IRAPe) is cleaved and secreted in the blood.

The plasmatic concentration of IRAPe is therefore proportional to its degree of expression and translocation to the membrane and should therefore be increased in proliferating tumours.

ELISA, IRMA and ICMA testing kits are currently in development.

We have already developed:

• 5 monoclonal antibodies targeting different IRAPe epitopes
• Recombinant human IRAPe
• Specific ligands that have been radioactively marked
• An ELISA prototype

Benefits

Our method is the first simple, specific and quantitative detection system for a direct marker of insulin resistance (IRAPe) in the blood.

The detection of IRAPe as well as the monoclonal antibodies and ligands are patented.

Applications

• Detection and medical prognosis of cancers
• Longterm analysis of insulin resistance and cancers

References

[1] Ito, T. et al. (1998) Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. Mod Pathol 11:437-443.
[2] Medina, R.A. et al. (2003) Estrogen and progesterone up-regulate glucose transporter expression in ZR-75-1 human breast cancer cells. Endocrinology 144: 4527-4535
[3] Keller, S.R. (2004) Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes. Biol Pharm Bull 27:761-764
[4] Shibata, K. et al. (2007) P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling. BMC Cancer 7: 15
[5] Pilar Carrera, M. et al. (2006) Insulin-regulated aminopeptidase/placenta leucil Aminopeptidase (IRAP/P-IAP) and angiotensin IV-forming activities are modified in serum of rats with breast cancer induced by N(methyl-nitrosourea. Anticancer Res 26: 1011-1014.

Contact
Véronique SENDRA
+33 (0)4 76 00 78 30
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