Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer
Prostate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DOcollagen I (a bone matrix protein) and, for comparison, DO-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, this degradation was reduced by inhibitors of matrix...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-03-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605800223 |
| _version_ | 1811262837026193408 |
|---|---|
| author | Izabela Podgorski Bruce E. Linebaugh Mansoureh Sameni Christopher Jedeszko Sunita Bhagat Michael L. Cher Bonnie F. Sloane |
| author_facet | Izabela Podgorski Bruce E. Linebaugh Mansoureh Sameni Christopher Jedeszko Sunita Bhagat Michael L. Cher Bonnie F. Sloane |
| author_sort | Izabela Podgorski |
| collection | DOAJ |
| description | Prostate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DOcollagen I (a bone matrix protein) and, for comparison, DO-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, this degradation was reduced by inhibitors of matrix metallo, serine, cysteine proteases. Because secretion of the cysteine protease cathepsin B is increased in human breast fibroblasts grown on collagen I gels, we analyzed cathepsin B levels and secretion in prostate cells grown on collagen I gels. Levels and secretion were increased only in DU145 cells-cells that expressed the highest baseline levels of cathepsin B. Secretion of cathepsin B was also elevated in DU145 cells grown in vitro on human bone fragments. We further investigated the effect of the bone microenvironment on cathepsin B expression and activity in vivo in a SCID-human model of prostate bone metastasis. High levels of cathepsin B protein and activity were found in DU145, PC3, LNCaP bone tumors, although the PC3 and LNCaP cells had exhibited low cathepsin B expression in vitro. Our results suggest that tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B. |
| first_indexed | 2024-04-12T19:34:07Z |
| format | Article |
| id | doaj.art-5a4cea8a4b4e49918af042475324eb4c |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T19:34:07Z |
| publishDate | 2005-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-5a4cea8a4b4e49918af042475324eb4c2022-12-22T03:19:15ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-03-017320722310.1593/neo.04349Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate CancerIzabela Podgorski0Bruce E. Linebaugh1Mansoureh Sameni2Christopher Jedeszko3Sunita Bhagat4Michael L. Cher5Bonnie F. Sloane6Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Urology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Urology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USAProstate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DOcollagen I (a bone matrix protein) and, for comparison, DO-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, this degradation was reduced by inhibitors of matrix metallo, serine, cysteine proteases. Because secretion of the cysteine protease cathepsin B is increased in human breast fibroblasts grown on collagen I gels, we analyzed cathepsin B levels and secretion in prostate cells grown on collagen I gels. Levels and secretion were increased only in DU145 cells-cells that expressed the highest baseline levels of cathepsin B. Secretion of cathepsin B was also elevated in DU145 cells grown in vitro on human bone fragments. We further investigated the effect of the bone microenvironment on cathepsin B expression and activity in vivo in a SCID-human model of prostate bone metastasis. High levels of cathepsin B protein and activity were found in DU145, PC3, LNCaP bone tumors, although the PC3 and LNCaP cells had exhibited low cathepsin B expression in vitro. Our results suggest that tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B.http://www.sciencedirect.com/science/article/pii/S1476558605800223Cathepsin Bbone microenvironmentprostate cancerosteolysistumor-stromal interactions |
| spellingShingle | Izabela Podgorski Bruce E. Linebaugh Mansoureh Sameni Christopher Jedeszko Sunita Bhagat Michael L. Cher Bonnie F. Sloane Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer Neoplasia: An International Journal for Oncology Research Cathepsin B bone microenvironment prostate cancer osteolysis tumor-stromal interactions |
| title | Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer |
| title_full | Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer |
| title_fullStr | Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer |
| title_full_unstemmed | Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer |
| title_short | Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer |
| title_sort | bone microenvironment modulates expression and activity of cathepsin b in prostate cancer |
| topic | Cathepsin B bone microenvironment prostate cancer osteolysis tumor-stromal interactions |
| url | http://www.sciencedirect.com/science/article/pii/S1476558605800223 |
| work_keys_str_mv | AT izabelapodgorski bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT bruceelinebaugh bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT mansourehsameni bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT christopherjedeszko bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT sunitabhagat bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT michaellcher bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer AT bonniefsloane bonemicroenvironmentmodulatesexpressionandactivityofcathepsinbinprostatecancer |