Understanding the Mechanism through which Matrix Metalloproteinases (MMPs) Contribute to Breast Cancer-Associated Osteolytic Lesions

2007 ◽  
Author(s):  
Sophie Thiolly
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinases ◽  
Osteolytic Lesions

Involvement of the co-receptor RAMP2 in the progression of breast cancer-induced osteolytic lesions

2013 ◽  
Author(s):  
Alfredo Cappariello ◽  
Nadia Rucci ◽  
Mattia Capulli ◽  
Maurizio Muraca ◽  
Anna Teti
Keyword(s):  
Breast Cancer ◽  
Osteolytic Lesions

scholarly journals Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions

Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Pantano ◽  
Martine Croset ◽  
Keltouma Driouch ◽  
Natalia Bednarz-Knoll ◽  
Michele Iuliani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Osteolytic Lesions ◽  
Cell Colonization

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

scholarly journals Matrix metalloproteinases in the process of invasion and metastasis of breast cancer

2006 ◽  
Vol 14 (3-4) ◽  
pp. 136-140 ◽  
Author(s):  
Gordana Konjevic ◽  
Sandra Stankovic
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Proteolytic Enzymes ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Collagen Type Iv ◽  
Cell Contact ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

Metastatic cascade in malignant tumors, including breast cancer, starts with localized invasion of the host tissue. This process, requiring that tumor cells separate from each other, includes loss of homotypic and heterotypic cell adhesion and cell-cell contact inhibition, acquisition of motility, exacerbated by "epithelial-to-mesenchymal transition", and production of proteolytic enzymes which degrade basal membrane and extracellular matrix. In this sense, aside from urokinase type plasminogen activator, increased expression and activity of matrix metalloproteinases (MMPs) is one of the earliest and most sustained events in tumor progression, playing a role in angiogenesis, invasion and metastasis. MMPs are a family of 23 zinc metalloproteinases, secreted as latent pro-enzymes, activated by proteolytic cleavage, and inhibited by the tissue inhibitors of metalloproteinases. The most commonly connected MMPs with the processes of metastasis are MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their ability to degrade collagen type IV, major component of vascular basement membrane. MMP-2 and MMP-9 are also required for the switch to the "angiogenic phenotype" during tumor progression and activation of dormant tumor cells. The association of the increase in serum MMP-2 and MMP-9 activity and clinical stage suggests the usefulness of these parameters as markers in the follow-up and prognosis of breast cancer patients. The concept of "stromal-directed therapy" of cancer, with MMP-inhibitors directed against MMPs as targets, is based on the observed MMP up-regulation in tumors.

scholarly journals MATRIX METALLOPROTEINASES AND THEIR ROLE IN BREAST CANCER: A MINI REVIEW

2019 ◽  
Vol 6 (1) ◽  
pp. 93-102
Author(s):  
Anamika Gupta ◽  
Rumana Ahmad ◽  
Shivbrat Upadhayay ◽  
A. N. Srivastava
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinases
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