Description

The study demonstrates that the expression of caveolin-1 (Cav1) in stromal cells generates an ordered and rigid extracellular environment, promoting tumour cell migration, as well as both local invasion and metastasis to distant organs, and hence tumour progression.
Thus, the present invention identifies a useful and reliable biological marker of tumour progression. The inventors have found that the increased expression of Cav1 in tumour-associated fibroblasts (TAFs) correlates with a worse prognosis, an increase in tumour progression, an increase in the invasive and metastatic capacity of the tumour, and worse patient survival.
The invention also describes a method for the diagnosis and/or prognosis of tumour progression, as well as the corresponding kit components. Moreover, the inventors have found that inhibition or the absence of Cav1 in the tumour microenvironment favours tumour encapsulation, thereby preventing tumour progression and metastasis. Therefore, the invention also indicates that Cav1 inhibitors can be used as medicines to prevent tumour progression.
Since the researchers have also determined the mechanism by which Cav1 influences the tumours extracellular environment, the invention describes agonists and antagonists of the molecules involved in the process that can be used as medicines to prevent tumour progression.

Innovations and advantages of the offer

So far, studies into the role of Cav1 in cancer have focused on its expression in tumour cells. The results obtained have been controversial because this protein is often only weakly expressed in primary tumours, although its expression may augment in very aggressive tumours and during the metastatic phase. The researchers found that stromal fibroblasts surrounding the tumoural tissue in the affected organs had more Cav1 than those surrounding non-cancerous tissues in the same organs. Furthermore, a correlation was found between the amount of Cav1 expressed by tumour-associated fibroblasts and metastasis, and the risk of early mortality.
Further deepening their understanding of this process, the research team found that the matrix ordering and rigidity generated by Cav1 is due to an increase in the activity of the Rho enzyme, which is the result of a complex series of events involving the inhibition of the natural Rho antagonist p190RhoGAP. Rho controls the contractile actomyosin filaments in the cell, producing elongated cells that stretch the stromal fibers creating a parallel and rigid structure that surrounds the tumoural cells and promotes metastasis.

Current and Potential Domain of Application

Oncology

Current Stage of Development

Development phase - Laboratory tested

Collaboration Type

License Agreement

Comments

Type of partner sought: clinical and pharmaceutical sector, mainly in oncology

Specific area of activity of the partner: Clinical trials, drugs development

Task to be performed by the partner sought: Development of diagnosis kits

Ref: 12 ES 28F8 3O2I