CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer.
- Zoni E Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- Chen L Department of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
- Karkampouna S Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- Granchi Z Genome Scan, Leiden, The Netherlands.
- Verhoef EI Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
- La Manna F Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- Kelber J Department of Biology, California State University Northbridge, Northbridge, CA, USA.
- Pelger RCM Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- Henry MD Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
- Snaar-Jagalska E Urology Research Laboratory, Department of Urology and Department of Clinical Research, University of Bern, Bern, Switzerland.
- van Leenders GJLH Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
- Beimers L Department of Orthopedic Surgery, Slotervaart Medical Center, Amsterdam, The Netherlands.
- Kloen P Department of Orthopedic Trauma Surgery, Academic Medical Center, Amsterdam, The Netherlands.
- Gray PC Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla CA, USA.
- van der Pluijm G Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- Kruithof-de Julio M Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
- 2017-04-11
Published in:
- Oncogene. - 2017
Animals
Bone Neoplasms
Cell Line, Tumor
Cell Movement
Cell Proliferation
GPI-Linked Proteins
Gene Knockdown Techniques
Heat-Shock Proteins
Humans
Intercellular Signaling Peptides and Proteins
Kaplan-Meier Estimate
Male
Mice
Mice, Nude
Neoplasm Proteins
Neoplasm Transplantation
Prostatic Neoplasms
English
CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1038/onc.2017.87
- PMID 28394345
- Persistent URL
- https://folia.unifr.ch/global/documents/166770
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