scholarly journals Cathepsin K and Its Specific Target in Mediating Breast Cancer Skeletal Metastasis

2020 ◽  
Vol 6 (2) ◽  
pp. 36-46
Author(s):  
Yaongamphi Vashum ◽  
Zenith Khashim ◽  
Fathima Bushra Sheriff M
Keyword(s):  
Breast Cancer ◽  
Cathepsin K ◽  
Skeletal Metastasis ◽  
Specific Target

Obesity and Cathepsin K: A Complex Pathophysiological Relationship in Breast Cancer Metastases

2020 ◽  
Vol 20 (8) ◽  
pp. 1227-1231
Author(s):  
Yaongamphi Vashum ◽  
Zenith Khashim
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Metastasis ◽  
Therapeutic Option ◽  
Metastatic Breast ◽  
Cathepsin K ◽  
Skeletal Metastasis ◽  
Breast Cancer Metastasis ◽  
Normal Weight ◽  
Breast Cancers

Background: Breast cancer appears in a strong inclination to metastasize in bone tissue. Several strategies are discussed in combating bone metastasis in breast cancer. However, therapy is only palliative and does not provide any improvement in survival to the majority of patients with advanced cancer. Obese and overweight women with breast cancer are three times more likely to develop metastatic disease compared to normal-weight women with the same treatment regimen. Overweight greatly intensify adipocytes formation in the bone marrow affecting bone metabolism by decreasing osteoblast differentiation and bone formation. Cathepsin K (CTSK), a cysteine protease, effectively degrades several components of the extracellular matrix and has the ability to differentiate adipocytes from bone marrow lineage. Therefore, the purpose of this review is to emphasize the underlying mechanism of CTSK and obesity role in breast cancer metastasis. Methods: Systematic review was performed using PubMed, EMBASE. The evidence of obesity and CTSK in breast cancer skeletal metastasis were analyzed, summarized and compared. Results: The present investigation argues for a specific association of CTSK with breast cancer skeletal metastasis by promoting adipocyte differentiation. The potential tumor-supporting roles of adipocytes are well documented, and in fact, suppressing adipocyte could be a new therapeutic option in the battle against lethal metastatic breast cancers. Conclusion: This review emphasizes CTSK through its multifaceted role in differentiating adipocytes, inflammation, and extracellular degradation, may be a critical factor in an obesity-cancer connection. Thus, integration of CTSK targeting strategies into established traditional therapies seems to hold substantial promise.

RANK expression on breast cancer cells promotes skeletal metastasis

2013 ◽  
Vol 31 (2) ◽  
pp. 233-245 ◽  
Author(s):  
Michelle L. Blake ◽  
Mark Tometsko ◽  
Robert Miller ◽  
Jon C. Jones ◽  
William C. Dougall
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Skeletal Metastasis

scholarly journals Conditional Knockdown of Osteopontin Inhibits Breast Cancer Skeletal Metastasis

2019 ◽  
Vol 20 (19) ◽  
pp. 4918 ◽  
Author(s):  
Marineta Kovacheva ◽  
Michael Zepp ◽  
Muriel Schraad ◽  
Stefan Berger ◽  
Martin R. Berger
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Skeletal Metastasis ◽  
Skeletal Metastases ◽  
Specific Gene ◽  
Cell Clones ◽  
Gene And Protein Expression ◽  
Metastasis Model ◽  
Breast Cancer Bone Metastasis

High osteopontin (OPN) expression is linked to breast cancer bone metastasis. In this study we modulated osteopontin levels conditionally and investigated any related antineoplastic effects. Therefore, we established cell clones from human breast cancer MDA-MB-231 cells, in which the expression of OPN is regulated by the Tet-Off tet-off system. These cells, which conditionally express a specific miRNA targeting OPN, were used for in vitro studies as well as for a bone metastasis model in nude rats. Changes in whole-genome expression elicited by conditional OPN knockdown and vesicle formation were also analyzed. The alkylphosphocholine erufosine was used for combination therapy. Conditional OPN knockdown caused mild anti-proliferative, but more intensive anti-migratory and anti clonogenic effects, as well as partial and complete remissions of soft tissue and osteolytic lesions. These effects were associated with specific gene and protein expression modulations following miRNA-mediated OPN knockdown. Furthermore, high levels of OPN were detected in vesicles derived from rats harboring breast cancer skeletal metastases. Finally, the combination of OPN inhibition and erufosine treatment caused an additive reduction of OPN levels in the investigated breast cancer cells. Thus, knockdown of OPN alone or in combination with erufosine is a promising strategy in breast cancer skeletal metastasis treatment.

Bone Microenvironment Tissue Surrogates Engineered for Reporting of Metastasized Breast Cancer Osteolytic Activity

2014 ◽  
Vol 1625 ◽  
Author(s):  
Jerald E. Dumas ◽  
Akia N. Parks ◽  
Manu O. Platt
Keyword(s):  
Breast Cancer ◽  
Bone Resorption ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Osteolytic Lesion ◽  
Cathepsin K ◽  
Mineral Dissolution ◽  
Bone Microenvironment ◽  
Metastatic Niche

ABSTRACTBreast cancer metastasis to bone continues to be a major clinical problem, and patient-to-patient variability in rates of disease progression and metastasis complicate treatment even further. This may be due to differences in the cancer cells, the osteoclasts, or the pre-metastatic niche, but all of these contribute to proteolytic remodeling necessary for osteolytic lesion establishment, primarily through secretion of cathepsin K, the most powerful human collagenase. There is debate about the relative contributions of breast cancer cells and osteoclasts and synergism between the two in altering the biochemical and biomechanical properties of the colonized bone, as these are difficult to parse with animal models. To quantify the relative contributions of breast cancer cells and osteoclasts in bone resorption, we have been developing engineered bone microenvironment tissue surrogates by adapting a poly(ester urethane) urea system embedded with microbone particles. Here, we report their use with MDA-MB-231 breast cancer cells and RAW264.7 derived osteoclasts, to provide temporal, multiscale reporters of bone resorption that can be measured non-destructively: 1) collagen degradation measured by C-terminal collagen fragment release, 2) mineral dissolution by measuring calcium released with the calcium arsenazo assay, and also show their beneficial effects in upregulating cathepsin K expression compared to tissue culture polystyrene controls. These more natural derived bone surrogates may be useful tools in mimicking bone metastatic niche and determining differences between proteolytic activity of different patients’ tumor and bone resident cells in a controlled manner.

scholarly journals Combined administration of a small-molecule inhibitor of TRAF6 and Docetaxel reduces breast cancer skeletal metastasis and osteolysis

2020 ◽  
Vol 488 ◽  
pp. 27-39 ◽  
Author(s):  
Ryan T. Bishop ◽  
Silvia Marino ◽  
Giovana Carrasco ◽  
Boya Li ◽  
Richard J. Allen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Small Molecule ◽  
Skeletal Metastasis ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor ◽  
Combined Administration

Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer

1992 ◽  
Vol 21 (2-4) ◽  
pp. 227-230 ◽  
Author(s):  
Jun-Ichi Yamashita ◽  
Kazuo Inada ◽  
Shin-Ichi Yamashita ◽  
Yasunari Nakashima ◽  
Shuichi Matsuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Human Breast Cancer ◽  
Skeletal Metastasis ◽  
Tissue Type ◽  
Human Breast ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Study comparing the concordance between PET/CT and bone scan in detecting skeletal metastasis in breast cancer patients.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e11122-e11122
Author(s):  
D. Landau ◽  
S. M. Constantino ◽  
S. Maddipatla ◽  
Z. J. Zhang ◽  
M. Hart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Bone Scan ◽  
Skeletal Metastasis ◽  
Breast Cancer Patients ◽  
Pet Ct

Lapatinib efficacy according to metastatic sites in trastuzumab pretreated patients with HER2-positive metastatic breast cancer: An analysis form IntERB registry in the Czech Republic.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11072-e11072 ◽  
Author(s):  
Peter Grell ◽  
Vit Kandrnal ◽  
Bortlicek Zbynek ◽  
Rostislav Vyzula
Keyword(s):  
Breast Cancer ◽  
Czech Republic ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Skin Toxicity ◽  
Skeletal Metastasis ◽  
Complete Response ◽  
Her2 Positive ◽  
Metastatic Sites

e11072 Background: Lapatinib is an oral dual tyrosin kinase inhibitor of EGFR and HER2 and compared to trastuzumab penetrates to CNS. We evaluated efficacy and safety of lapatinib treatment according to different metastatic sites involvement using data from IntERB registry that has been initiated and run by Czech Society for Oncology and Institute of Biostatistics and Analyses at Masaryk University, Brno, Czech Republic. Methods: An analysis included 213 patients with HER2 positive metastatic breast cancer treated from January 2007 to September 2011. Lapatinib was mostly administered orally 1250mg/day with capecitabine (2000mg/m2 D1-14), 16 patients received lapatinib in monotherapy. All patients had experienced progression during prior trastuzumab based therapy. Results: Median age was 56 years (range 23 – 78). Median duration of lapatinib therapy was 20.6 weeks (range 1–146). Complete response was achieved in 13 patients (6.1%), partial response in 31 (14.6%), stable disease in 118 (55.4%). In 26 disease have progressed (12.2%); response could not be assessed in 25 patients (11.7%). PFS for whole group was 7.1 months (95% CI 5.9-8.5). Overall survival was 17.2m (95% CI 15.8-18.6), probability of 6m OS was 80.3% and 1-year OS was 64%. Metastatic sites specific survival was evaluated in 103 patients. CNS dissemination was initially diagnosed in 31 patients (30.1%), PFS in this group was 6.2m (95% CI 3.3-9.1), OS was not reached, 6-m OS was 67.3%. In non-CNS group (skeletal metastasis in 49.5%, lung 38.8%, hepatic 36.9%, lymphatic 17.5%, other 15.5%) was PFS 6.3m (95% CI 1.6-11.1), OS 22.0m (95% CI 15.3-28.8) and 6-m OS was 88.2%. Most common toxicities were diarrhea in 11.7% patients, rash/skin toxicity in 10.8%, nausea/vomitus in 5.2% and hepatotoxicity in 2.3%. No cardiac toxicity was reported. Therapy was discontinued due toxicity in 9.0%. Conclusions: Lapatinib in combination with capecitabine proved its efficacy in trastuzumab pretreated HER2 positive metastatic breast cancer. Even in patients with CNS involvement was achieved a notable PFS and OS, comparable to non-CNS group of patients. Therapy was well tolerated.

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