RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones.

Abstract

BACKGROUND:

Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides.

METHODS:

Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting

RESULTS:

When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 mum pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides.

CONCLUSION:

Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC.

• Authors: Marco Della Peruta, Cinzia Giagulli, Carlo Laudanna, Aldo Scarpa, Claudio Sorio
• Journal: Molecular cancer (Mol Cancer) Vol. 9 Pg. 61 (Mar 17 2010) ISSN: 1476-4598 [Electronic] England
• PMID: 20236512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• protein kinase C zeta
• Protein Kinase C
• rhoA GTP-Binding Protein

Topics

• Animals
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Membrane Permeability (drug effects)
• Cell Movement (drug effects)
• Cell Shape (drug effects)
• Clone Cells
• Lung Neoplasms (enzymology, secondary)
• Mice
• Mice, Nude
• Pancreatic Neoplasms (enzymology, pathology)
• Peptides (pharmacology)
• Protein Kinase C (genetics, metabolism)
• Wound Healing (drug effects)
• rhoA GTP-Binding Protein (genetics, metabolism)