Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Olivares-Urbano, María Auxiliadora; Griñán‐Lisón, Carmen; Zurita, Mercedes; Moral, R. Del; Ríos‐Arrabal, Sandra; Artacho‐Cordón, Francisco; Arrebola, Juan Pedro; A, González; León, Josefa; Marchal, Juan A.; Núñez, María Isabel

doi:10.1111/jcmm.14671

Cited by 19 publications

(13 citation statements)

References 51 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, MMP-2 and MMP-9 proteolytic activity was increased with increasing radiation doses, suggesting that matrix degradation does continue to occur. The elevation of MMP activity after radiation exposure has already been extensively reported in patients receiving radiotherapy for various types of cancer, including breast cancer and malignant gliomas (40)(41)(42). Our findings are therefore in line with other studies that examined the effects of radiation on MMP function.…”

Section: Discussionsupporting

confidence: 91%

Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease

Meerman

Driessen

Engeland

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Background: Mediastinal ionizing radiotherapy is associated with an increased risk of valvular disease, which demonstrates pathological hallmarks similar to calcific aortic valve disease (CAVD). Despite advances in radiotherapy techniques, the prevalence of comorbidities such as radiation-associated valvular disease is still increasing due to improved survival of patients receiving radiotherapy. However, the mechanisms of radiation-associated valvular disease are largely unknown. CAVD is considered to be an actively regulated disease process, mainly controlled by valvular interstitial cells (VICs). We hypothesize that radiation exposure catalyzes the calcific response of VICs and, therefore, contributes to the development of radiation-associated valvular disease.Methods and Results: To delineate the relationship between radiation and VIC behavior (morphology, calcification, and matrix turnover), two different in vitro models were established: (1) VICs were cultured two-dimensional (2D) on coverslips in control medium (CM) or osteogenic medium (OM) and irradiated with 0, 2, 4, 8, or 16 Gray (Gy); and (2) three-dimensional (3D) hydrogel system was designed, loaded with VICs and exposed to 0, 4, or 16 Gy of radiation. In both models, a dose-dependent decrease in cell viability and proliferation was observed in CM and OM. Radiation exposure caused myofibroblast-like morphological changes and differentiation of VICs, as characterized by decreased αSMA expression. Calcification, as defined by increased alkaline phosphatase activity, was mostly present in the 2D irradiated VICs exposed to 4 Gy, while after exposure to higher doses VICs acquired a unique giant fibroblast-like cell morphology. Finally, matrix turnover was significantly affected by radiation exposure in the 3D irradiated VICs, as shown by decreased collagen staining and increased MMP-2 and MMP-9 activity.Conclusions: The presented work demonstrates that radiation exposure enhances the calcific response in VICs, a hallmark of CAVD. In addition, high radiation exposure induces differentiation of VICs into a terminally differentiated giant-cell fibroblast. Further studies are essential to elucidate the underlying mechanisms of these radiation-induced valvular changes.

show abstract

Section: Discussionsupporting

confidence: 91%

Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease

Meerman

Driessen

Engeland

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…The balance between MMPs and their tissue inhibitors (TIMPs) plays a crucial role in cancer progression and metastasis [23]. Our previous work has shown the involvement of MMP-3, MMP-9, TIMP-3, and TIMP-4 in response to radiotherapy in breast cancer patients, suggesting their utility as potential prognostic and predictive biomarkers for this pathology [24]. In breast cancer, several strategies for the development of inhibitors with therapeutic potential targeting the MMPs were discussed by Radisky et al [11,19].…”

Section: Introductionmentioning

confidence: 99%

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development

Camacho

Ramírez²,

Pérez-Alonso

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%–>50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control–case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.

show abstract

“…Ets-1, an important transcription factor for regulating the invasion and metastasis of tumors, has a binding site on the MMP9 promoter (29), explaining the role of MMP9 in promoting the invasion of breast cancer. A recent study reported that MMP1-induced brain metastasis of breast cancer is related to the downregulation of non-coding RNAMiR-202-3p expression in brain metastases (30). While investigating treatments for breast cancer, Olivares-Urbano et al found that serum levels of tissue inhibitors of MMP1 and MMP3 (TIMP-1 and TIMP-3) were reduced following radiotherapy and inversely proportional to the 30-minute treatment time, which provided a new basis for predicting radiotherapy toxicity.…”

Section: Discussionmentioning

confidence: 99%

A perspective of matrix metalloproteases gene expression profile revealed by pan-cancer transcriptome and single cell data

Tan

Wang

Gao

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Matrix metalloproteases (MMPs) are encoded by a family of genes that are related to cancer progression, and the overexpression of most MMP genes in cancers is associated with the promotion of invasion, angiogenesis, and immune surveillance avoidance. However, the expression patterns of all MMP genes at the transcriptome and single-cell levels have not been investigated from a pan-cancer perspective. Methods: The Cancer Genome Atlas transcriptome and single-cell sequencing pan-cancer data from the Gene Expression Omnibus were used in the present study to examine the expression patterns of these genes. The MMP-based diagnostic model was constructed using least absolute shrinkage and selection operator regression analysis. Tumors were classified into high and low score MMP groups using ssGSEA. Single-cell data were analyzed using the Seurat R package, and MMP gene expression was validated using quantitative real-time polymerase chain reaction.Results: MMP1, MMP11, and MMP12 expression was upregulated in almost all cancers. MMP19 and MMP27 expression was significantly downregulated in eight to nine cancer types. Correlation analysis results suggested a relationship between MMP expression and tumor immunity and stemness. Single-cell analysis results revealed diverse MMP expression patterns in different cell clusters. Conclusion: The majority of MMPs showed increased expression across cancers, with potential diagnostic value.

show abstract

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Cited by 19 publications

References 51 publications

Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease

Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development

A perspective of matrix metalloproteases gene expression profile revealed by pan-cancer transcriptome and single cell data

Contact Info

Product

Resources

About