Séminaire de Julien Duez le 07 juin

Invité par l’équipe 4 le Dr Julien Duez donnera un séminaire « Pharmacological stiffening of cancer stem cells to prevent tumor dissemination. » le 07 juin prochain au CRCINA à partir de 11h30, amphithéâtre Denis Escande, 8 quai Moncousu à Nantes.

Résumé :

Cancer-stem cells (CSC) are believed to represent an outnumbered population of cancer cells driving tumour growth and recurrence.

Whilst most scientific attention is centered on « how to detect/select CSC in routine and kill these ? », only three studies have focused on CSC deformability. Interestingly, these studies showed that CSC (from melanoma, breast and ovarian cancer cell lines) are more deformable than their differentiated counterpart. The high deformability of CSC appears crucial to support their efficient extravasation. Moreover, CSC deformability can be reversed by targeted pharmacological treatments that impacts cytoskeleton architecture, what abrogates CSC invasiveness. These findings open the perspective of developing drugs which stiffen CSC to prevent tumor dissemination. However, new studies are needed for a complete extrapolation of these results to the human level and to other cancers, and to validate druggable targets of pharmaceutical interest.

The recent discovery that deformability is essential for cancer cells to compete for survival by cell cannibalism also raises the question: « Are CSC also cannibal and then, does CSC stiffening may prevent this ? »

Until recently, studies on CSC deformability have been heavily challenged by the low throughput of current methods available in the field. Cell filtration across microsphere layers (microsphiltration) has just filled this biotechnological gap, by enabling to assess the deformability of thousands cell samples in a single experiment, opening the way to innovative diagnostic and drug discovery approaches.

This project aims to set up microsphiltration of CSC and establish in vitro and mice models of CSC cannibalism, extravasation and metastasis, confirm the causal relationship between CSC deformability, survival and invasiveness, clarify the associated signalling networks and provide/use an unprecedented screening platform enabling to select CSC mechanomodulators with anticancer properties.

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