CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer
| Autor: | Peter Kloen, Sofia Karkampouna, Rob C.M. Pelger, G J L H van Leenders, Lijkele Beimers, Zoraide Granchi, E Snaar-Jagalska, F. La Manna, Lanpeng Chen, M D Henry, Eugenio Zoni, Esther I. Verhoef, Peter C. Gray, M. Kruithof-De Julio, G. van der Pluijm, Jonathan A. Kelber |
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| Přispěvatelé: | Pathology, Other departments, APH - Personalized Medicine, APH - Quality of Care, Orthopedic Surgery and Sports Medicine, AMS - Restoration & Development, AMS - Ageing & Morbidty, Other Research |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Mice Nude Bone Neoplasms Kaplan-Meier Estimate Biology Cripto GPI-Linked Proteins Molecular oncology Metastasis 03 medical and health sciences Prostate cancer Mice Growth factor receptor SDG 3 - Good Health and Well-being Cell Movement Cell Line Tumor Genetics medicine Animals Humans Molecular Biology Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Cell Proliferation Cancer Bone metastasis Prostatic Neoplasms medicine.disease Neoplasm Proteins 030104 developmental biology Gene Knockdown Techniques Immunology Cancer cell Cancer research Intercellular Signaling Peptides and Proteins Original Article hormones hormone substitutes and hormone antagonists Neoplasm Transplantation |
| Zdroj: | Oncogene, 36(33), 4739-4749. Nature Publishing Group Oncogene Oncogene, 36(33), 4739-4749. NATURE PUBLISHING GROUP Oncogene, 36, 4739-4749 |
| ISSN: | 0950-9232 4739-4749 |
| Popis: | 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 ALDH(high) sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDH(low). 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 ALDH(high) sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDH(high) 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. |
| Databáze: | OpenAIRE |
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