Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer
Sulf-2 is an endosulfatase with activity against glucosamine-6-sulfate modifications within subregions of intact heparin. The enzyme has the potential to modify the sulfation status of extracellular heparan sulfate proteoglycan (HSPG) glycosaminoglycan chains and thereby to regulate interactions wit...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-11-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605800351 |
| _version_ | 1818346624694353920 |
|---|---|
| author | Megumi Morimoto-Tomita Kenji Uchimura Annette Bistrup David H. Lum Mikala Egeblad Nancy Boudreau Zena Werb Steven D. Rosen |
| author_facet | Megumi Morimoto-Tomita Kenji Uchimura Annette Bistrup David H. Lum Mikala Egeblad Nancy Boudreau Zena Werb Steven D. Rosen |
| author_sort | Megumi Morimoto-Tomita |
| collection | DOAJ |
| description | Sulf-2 is an endosulfatase with activity against glucosamine-6-sulfate modifications within subregions of intact heparin. The enzyme has the potential to modify the sulfation status of extracellular heparan sulfate proteoglycan (HSPG) glycosaminoglycan chains and thereby to regulate interactions with HSPG-binding proteins. In the present investigation, data mining from published studies was employed to establish Sulf-2 mRNA upregulation in human breast cancer. We further found that cultured breast carcinoma cells expressed Sulf-2 mRNA and released enzymatically active proteins into conditioned medium. In two mouse models of mammary carcinoma, Sulf-2 mRNA was upregulated in comparison to its expression in normal mammary gland. Although mRNA was present in normal tissues, Sulf-2 protein was undetectable; it was, however, detected in some premalignant lesions and in tumors. The protein was localized to the epithelial cells of the tumors. In support of the possible mechanistic relevance of Sulf- 2 upregulation in tumors, purified recombinant Sulf-2 promoted angiogenesis in the chick chorioallantoic membrane assay. |
| first_indexed | 2024-12-13T17:21:14Z |
| format | Article |
| id | doaj.art-4cd5923c5912493783a86e7f2c2ef76f |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-13T17:21:14Z |
| publishDate | 2005-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4cd5923c5912493783a86e7f2c2ef76f2022-12-21T23:37:18ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-11-017111001101010.1593/neo.05496Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast CancerMegumi Morimoto-Tomita0Kenji Uchimura1Annette Bistrup2David H. Lum3Mikala Egeblad4Nancy Boudreau5Zena Werb6Steven D. Rosen7Department of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USAThios Pharmaceuticals, 5980 Horton Street, Emeryville, CA 94608, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USADepartment of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0452, USASulf-2 is an endosulfatase with activity against glucosamine-6-sulfate modifications within subregions of intact heparin. The enzyme has the potential to modify the sulfation status of extracellular heparan sulfate proteoglycan (HSPG) glycosaminoglycan chains and thereby to regulate interactions with HSPG-binding proteins. In the present investigation, data mining from published studies was employed to establish Sulf-2 mRNA upregulation in human breast cancer. We further found that cultured breast carcinoma cells expressed Sulf-2 mRNA and released enzymatically active proteins into conditioned medium. In two mouse models of mammary carcinoma, Sulf-2 mRNA was upregulated in comparison to its expression in normal mammary gland. Although mRNA was present in normal tissues, Sulf-2 protein was undetectable; it was, however, detected in some premalignant lesions and in tumors. The protein was localized to the epithelial cells of the tumors. In support of the possible mechanistic relevance of Sulf- 2 upregulation in tumors, purified recombinant Sulf-2 promoted angiogenesis in the chick chorioallantoic membrane assay.http://www.sciencedirect.com/science/article/pii/S1476558605800351extracellular endosulfataseSulf-2breast cancerangiogenesisheparan sulfate |
| spellingShingle | Megumi Morimoto-Tomita Kenji Uchimura Annette Bistrup David H. Lum Mikala Egeblad Nancy Boudreau Zena Werb Steven D. Rosen Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer Neoplasia: An International Journal for Oncology Research extracellular endosulfatase Sulf-2 breast cancer angiogenesis heparan sulfate |
| title | Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer |
| title_full | Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer |
| title_fullStr | Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer |
| title_full_unstemmed | Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer |
| title_short | Sulf-2, a Proangiogenic Heparan Sulfate Endosulfatase, Is Upregulated in Breast Cancer |
| title_sort | sulf 2 a proangiogenic heparan sulfate endosulfatase is upregulated in breast cancer |
| topic | extracellular endosulfatase Sulf-2 breast cancer angiogenesis heparan sulfate |
| url | http://www.sciencedirect.com/science/article/pii/S1476558605800351 |
| work_keys_str_mv | AT megumimorimototomita sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT kenjiuchimura sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT annettebistrup sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT davidhlum sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT mikalaegeblad sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT nancyboudreau sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT zenawerb sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer AT stevendrosen sulf2aproangiogenicheparansulfateendosulfataseisupregulatedinbreastcancer |