The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells
Abstract
Bone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined. In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient–derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependent inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angiopoietin 1 (Ang1), and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu. (Cancer Res 2006; 66(1): 184-91)
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Cited by
Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets
Hideshima, T., Mitsiades, C., Tonon, G., Richardson, P. G., & Anderson, K. C. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2189 · Cited by 932
Self-citationHypoxia signalling through mTOR and the unfolded protein response in cancer
Wouters, B. G., & Koritzinsky, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2501 · Cited by 894
Antitumor Activity of PR-171, a Novel Irreversible Inhibitor of the Proteasome
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Vascular Endothelial Growth Factor and Its Relationship to Inflammatory Mediators
Angelo, L. S., & Kurzrock, R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2416 · Cited by 295
Hideshima, T., Richardson, P. G., & Anderson, K. C. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0433 · Cited by 265
Self-citation
Metadata
- Authors
- Roccaro, A. M., Hideshima, T., Raje, N., Kumar, S., Ishitsuka, K., Yasui, H., Shiraishi, N., Ribatti, D., Nico, B., Vacca, A., Dammacco, F., Richardson, P. G., & Anderson, K. C.
- Venue
- Cancer Research
- Published
- 2006-01-01
- Volume
- 66
- Issue
- 1
- Pages
- 184-191
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2158794607
- Cited by
- 284
- References
- 47
- FWCI
- 13.69
- Type
- journal article
- Language
- en
- Open access
- closed
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- Roccaro, A. M., Hideshima, T., Raje, N., Kumar, S., Ishitsuka, K., Yasui, H., Shiraishi, N., Ribatti, D., Nico, B., Vacca, A., Dammacco, F., Richardson, P. G., & Anderson, K. C. (2006). Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-05-1195
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