The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer
Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models reca...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558612800133 |
| _version_ | 1811277400619614208 |
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| author | Nader Al Nakouzi Olivia Bawa Alain Le Pape Stéphanie Lerondel Catherine Gaudin Paule Opolon Patrick Gonin Karim Fizazi Anne Chauchereau |
| author_facet | Nader Al Nakouzi Olivia Bawa Alain Le Pape Stéphanie Lerondel Catherine Gaudin Paule Opolon Patrick Gonin Karim Fizazi Anne Chauchereau |
| author_sort | Nader Al Nakouzi |
| collection | DOAJ |
| description | Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging. The IGR-CaP1 tumors grew when subcutaneously injected or when orthotopically implanted, reconstituted the prostate adenocarcinoma with glandular acini-like structures, and could disseminate to the liver and lung. Bone lesions were detected using bioluminescence imaging after direct intratibial or intracardiac injections. Anatomic bone structure assessed using high-resolution computed tomographic scans showed both lytic and osteoblastic lesions. Technetium Tc 99m methylene diphosphonate micro single-photon emission computed tomography confirmed the mixed nature of the lesions and the intensive bone remodeling. We also identified an expression signature for responsiveness of IGR-CaP1 cells to the bone microenvironment, namely expression of CXCR4, MMP-9, Runx2, osteopontin, osteoprotegerin, ADAMTS14, FGFBP2, and HBB. The IGR-CaP1 cell line is a unique model derived from a primary tumor, which can reconstitute human prostate adenocarcinoma in animals and generate experimental bone metastases, providing a novel means for understanding the mechanisms of bone metastasis progression and allowing preclinical testing of new therapies. |
| first_indexed | 2024-04-13T00:15:04Z |
| format | Article |
| id | doaj.art-b01ee839269e4a79a3ad93f08799154e |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T00:15:04Z |
| publishDate | 2012-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-b01ee839269e4a79a3ad93f08799154e2022-12-22T03:10:57ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022012-05-0114537638710.1593/neo.12308The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate CancerNader Al Nakouzi0Olivia Bawa1Alain Le Pape2Stéphanie Lerondel3Catherine Gaudin4Paule Opolon5Patrick Gonin6Karim Fizazi7Anne Chauchereau8Prostate Cancer Group, INSERM U981, Institut Gustave Roussy, Villejuif, FranceUniversity Paris-Sud 11, FranceUPS44 TAAM-CIPA, CNRS, Orléans, FranceUPS44 TAAM-CIPA, CNRS, Orléans, FranceProstate Cancer Group, INSERM U981, Institut Gustave Roussy, Villejuif, FranceUniversity Paris-Sud 11, FranceUniversity Paris-Sud 11, FranceProstate Cancer Group, INSERM U981, Institut Gustave Roussy, Villejuif, FranceProstate Cancer Group, INSERM U981, Institut Gustave Roussy, Villejuif, FranceBone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging. The IGR-CaP1 tumors grew when subcutaneously injected or when orthotopically implanted, reconstituted the prostate adenocarcinoma with glandular acini-like structures, and could disseminate to the liver and lung. Bone lesions were detected using bioluminescence imaging after direct intratibial or intracardiac injections. Anatomic bone structure assessed using high-resolution computed tomographic scans showed both lytic and osteoblastic lesions. Technetium Tc 99m methylene diphosphonate micro single-photon emission computed tomography confirmed the mixed nature of the lesions and the intensive bone remodeling. We also identified an expression signature for responsiveness of IGR-CaP1 cells to the bone microenvironment, namely expression of CXCR4, MMP-9, Runx2, osteopontin, osteoprotegerin, ADAMTS14, FGFBP2, and HBB. The IGR-CaP1 cell line is a unique model derived from a primary tumor, which can reconstitute human prostate adenocarcinoma in animals and generate experimental bone metastases, providing a novel means for understanding the mechanisms of bone metastasis progression and allowing preclinical testing of new therapies.http://www.sciencedirect.com/science/article/pii/S1476558612800133 |
| spellingShingle | Nader Al Nakouzi Olivia Bawa Alain Le Pape Stéphanie Lerondel Catherine Gaudin Paule Opolon Patrick Gonin Karim Fizazi Anne Chauchereau The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer Neoplasia: An International Journal for Oncology Research |
| title | The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer |
| title_full | The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer |
| title_fullStr | The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer |
| title_full_unstemmed | The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer |
| title_short | The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer |
| title_sort | igr cap1 xenograft model recapitulates mixed osteolytic blastic bone lesions observed in metastatic prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1476558612800133 |
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