| Title |
Cathepsin L in tumor angiogenesis and its therapeutic intervention by the small molecule inhibitor KGP94
|
|---|---|
| Published in |
Clinical & Experimental Metastasis, April 2016
|
| DOI | 10.1007/s10585-016-9790-1 |
| Pubmed ID | |
| Authors |
Dhivya R. Sudhan, Maria B. Rabaglino, Charles E. Wood, Dietmar W. Siemann |
| Abstract |
A significant proportion of breast cancer patients harbor clinically undetectable micrometastases at the time of diagnosis. If left untreated, these micro-metastases may lead to disease relapse and possibly death. Hence, there is significant interest in the development of novel anti-metastatic agents that could also curb the growth of pre-established micrometastases. Like primary tumor, the growth of metastases also is driven by angiogenesis. Although the role of cysteine protease Cathepsin L (CTSL) in metastasis associated tumor cell functions such as migration and invasion is well recognized, its role in tumor angiogenesis remains less explored. The present study examines the contribution of CTSL to breast cancer angiogenesis and evaluates the anti-angiogenic efficacy of CTSL inhibitor KGP94. CTSL semi-quantitative RT-PCR analysis on breast tissue panels revealed significant upregulation of CTSL in breast cancer patients which strongly correlated with increased relapse and metastatic incidence and poor overall survival. Preclinically, CTSL ablation using shRNA or KGP94 treatment led to a significant reduction in MDA-MB-231 tumor cell induced angiogenesis in vivo. In-vitro assessments demonstrated a significant decrease in various angiogenic properties such as endothelial cell sprouting, migration, invasion, tube formation and proliferation in the presence of KGP94. Microarray analyses revealed a significant upregulation of cell cycle related genes by CTSL. Western blot analyses further confirmed upregulation of members of the cyclin family by CTSL. Collectively, these data indicate that CTSL is an important contributor to tumor angiogenesis and that the CTSL inhibition may have therapeutic utility in the treatment of breast cancer patients. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 41 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 22% |
| Student > Doctoral Student | 5 | 12% |
| Student > Ph. D. Student | 5 | 12% |
| Student > Master | 3 | 7% |
| Researcher | 2 | 5% |
| Other | 3 | 7% |
| Unknown | 14 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 27% |
| Medicine and Dentistry | 4 | 10% |
| Agricultural and Biological Sciences | 3 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Unspecified | 2 | 5% |
| Other | 5 | 12% |
| Unknown | 14 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 April 2016.
All research outputs
#18,698,308
of 23,854,458 outputs
Outputs from Clinical & Experimental Metastasis
#575
of 778 outputs
Outputs of similar age
#210,657
of 304,264 outputs
Outputs of similar age from Clinical & Experimental Metastasis
#6
of 11 outputs
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