Matrix metalloproteinases: Potential therapy to prevent the development of second malignancies after breast radiotherapy

Artacho‐Cordón, Francisco; Ríos‐Arrabal, Sandra; Lara, Pedro C.; Artacho-Cordón, Antonia; Calvente, Irene; Núñez, M.I.

doi:10.1016/j.suronc.2012.06.001

Cited by 67 publications

(54 citation statements)

References 91 publications

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“…Metalloproteinase-1 (MMP-1) is collagen involved in the angiogenesis that is secreted by the effects of oxidative stress and increases the stimulation of growth in tumor blood vessels. MMP-2 is another member of the metalloproteinase family that is activated by the reaction of the thiol group with ROS; it has an important role in the metastasis of breast cancer cells (Rajagopalan et al, 1996;Brown et al, 2000;Artacho-Cordon et al, 2012). Another metalloproteinase is MMP-3 protein.…”

Section: Oxidative Stress and Breast Cancermentioning

confidence: 99%

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

Nourazarian¹,

Kangari²,

Salmaninejad³

2014

Asian Pacific Journal of Cancer Prevention

150

108

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Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

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Section: Oxidative Stress and Breast Cancermentioning

confidence: 99%

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

Nourazarian¹,

Kangari²,

Salmaninejad³

2014

Asian Pacific Journal of Cancer Prevention

150

108

View full text Add to dashboard Cite

show abstract

“…The invasive behavior of cancer cells and their ability to metastasize to a distant location are multiple step processes associated with the detachment of cells from the original cancer, attachment to extracellular matrix (ECM) binding sites, degradation of the ECM and migration to target tissues (13). One of the critical steps involved in metastasis is the activity of MMPs that degrade a variety of ECM proteins (14).…”

Section: Introductionmentioning

confidence: 99%

Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

Jin

Park

Kim

et al. 2013

International Journal of Oncology

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Abstract. Halofuginone (HF) is extracted from Dichroa febrifuga, a plant used in traditional medicine. We report that the HF extract inhibits the growth of breast cancer cells and induces the generation of reactive oxygen species (ROS) and apoptosis, an important feature of potential anticancer agents. In addition, HF significantly reduces the migration and invasion of MCF-7 and MDA-MB-231 human breast cancer cells after 12-O-tetraecanoylphorbol-13-acetate (TPA) stimulation. As matrix metalloproteinase-9 plays a critical role in tumor metastasis, we analyzed its expression with the HF extract treatment. Western blot analysis and gelatin zymography showed that HF suppresses MMP-9 expression and activity concentrationdependently. HF also decreases the nuclear protein levels of nuclear factor kappa B (NF-κB) and c-fos (AP-1), critical transcription factors regulating MMP-9 expression through binding the MMP-9 promoter region. Luciferase assays showed that HF decreases TPA-induced MMP-9 promoter binding activities of NF-κB and AP-1. Taken together, these are the first results indicating that halofuginone may represent a promising new agent for breast cancer chemotherapy.

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“…2,3 Indeed, metastasis in breast cancer can be undetectable and remain dormant for many years after the removal of the primary tumor, contributing to the poor survival and low life expectancy of these patients. 4 Many steps are involved in this process, and other authors have described that chemokines, 5,6 adhesion proteins, 7 and metalloproteinases [8][9][10] are the most important molecules for the migration of breast cancer cells and establishment of metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…A loss of control of MMPs can result in pathological processes including inflammation, angiogenesis, cellular proliferation 11,12 and are directly involved in the metastatic tumor cell invasion process. 9 Among them, gelatinase A (MMP-2) is associated with a malignant phenotype, as it is responsible for the degradation of collagen fibers around tumors, thereby releasing these cells from the microenvironment in which they are established. This function is directly involved in the progress of metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors

Ramos

Silva

Manica

et al. 2016

Rev. Assoc. Med. Bras.

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Introduction: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR). Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy. Objective: To study the correlation among MMP-2, ER, and PR, as well as the establishment of the metastatic process in primary breast tumors. Method: Breast cancer samples (n=44) were analyzed by immunohistochemistry for MMP-2, ER, and PR. Results: We observed that 90% of patients who had metastases and died showed positive staining for MMP-2 (p=0.0082 for both). Using Kaplan-Meier analysis, we found that negative ER patients who were also positive for MMP-2 had even worse disease-free survival (DFS) and overall survival (OS) (p= 0.012 and p=0.005, respectively). Similar results were found in PR-negative patients for DFS (a trend p=0.077) and OS (p=0.038). Conclusion: Regardless of our small sample size (n=44), the data obtained strongly suggest that MMP-2 in combination with already well-established markers could help to predict the emergence of metastases and death in patients with breast cancer.

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Matrix metalloproteinases: Potential therapy to prevent the development of second malignancies after breast radiotherapy

Cited by 67 publications

References 91 publications

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors

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