Low microvascular density at the tumor center is related to the expression of metalloproteases and their inhibitors and with the occurrence of distant metastasis in breast carcinomas

Fernández-Guinea, Óscar; Alvarez-Cofiño, Almudena; Eiró, Noemí; González, Luis O.; Casar, José M. del; Fernández-García, Belén; Lamelas, Marı́a L.; Andicoechea, Alejandro

doi:10.1007/s10147-012-0428-2

Cited by 10 publications

(8 citation statements)

References 52 publications

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“…We compiled clinical data, data from animal models and theoretical data taken from literature in the columns “Clin./Lit.” for normal (left) and tumor tissue (last col.), respectively. Microvascular density obtained by our model and from [7] is given as the line density L D whereas data from [85, 86] are the medians of histological MVD . rBF scaled is the initial tissue rBF scaled by the ratio of perfusions, rBF , of the iso-volumetric tumor sphere at t = 0 and at t = 600 h (see text).…”

Section: Resultsmentioning

confidence: 99%

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

et al. 2016

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We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors.

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Section: Resultsmentioning

confidence: 99%

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

et al. 2016

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“…Univariate survival analysis data for OS were available in 16 studies, which included 9 studies with MMP-9 [ 8 – 10 , 14 , 27 , 29 , 31 , 33 , 34 ] and 5 studies with MMP-2 [ 11 , 12 , 15 , 25 , 27 , 31 , 32 ]. For the overall population, worse OS was observed among patients with MMPs overexpression (HR = 1.577, 95%CI: 1.216–2.045, P = 0.001) ( Fig 2 ) in the 16 studies.…”

Section: Resultsmentioning

confidence: 99%

“…The relationship between OS and MMP-9 up-regulation was analyzed in nine studies by univariate analysis [ 8 – 10 , 14 , 27 , 29 , 31 , 33 , 34 ]. The pooled HR was 1.404 (95%CI: 0.903–2.181, P = 0.131) and heterogeneity existed (P heterogeneity = 0.017, I 2 = 57.1%) ( Fig 5 ).…”

Section: Resultsmentioning

confidence: 99%

Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

et al. 2015

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BackgroundMatrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients.MethodA systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsA total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347–2.129, P < 0.001; HR = 1.611, 95%CI: 1.419–1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460–2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330–2.420, P < 0.001) and 1.709 (95%CI: 1.157–2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610–3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065–2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis.ConclusionsOur findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression.

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“…At present, there are 28 protein members in the MMP family. They can be divided into the following subgroups which include collagenase and gelatinase, interstitial lysins, and membrane‐type MMPs . MMP‐11 was first discovered by Basset et al .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐125b as a tumor suppressor by targeting MMP11 in breast cancer

et al. 2020

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Background: Breast cancer is a common type of tumor in women worldwide. MicroRNAs have been identified as regulators in many human cancers. The aim of this study was therefore to investigate the functional role of miR-125b in regulating breast cancer progression. Methods: We used the StarBase database to investigate the expression of miRNA-125b in breast cancer and adjacent normal tissues. MMP11 3 0 -UTR construct and luciferase reporter assays was performed for target genes. Cell proliferation was evaluated by CCK-8 and colony formation assay. The migration and invasion were assessed by transwell assay. Results: Luciferase reporter assays showed miRNA-125b directly targeted MMP11. miRNA-125b by transfection with its mimic in breast cancer cells significantly suppressed breast cancer cell proliferation and migration. Western blot revealed that overexpression of miRNA-125b substantially reduced MMP11 protein expression. We used the UALCAN database to investigate the expression of MMP11 in human breast cancer and adjacent normal tissues. In addition, we found that miRNA-125b spoiled MMP11 induced breast cancer cell proliferation and migration promotion effect. Conclusions: miRNA-125b mimic inhibited proliferation, migration, and invasion of breast cancer cells through targeting MMP11 protein.

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Low microvascular density at the tumor center is related to the expression of metalloproteases and their inhibitors and with the occurrence of distant metastasis in breast carcinomas

Abstract: Our data point out the clinical importance of low MVD at the tumor center as an independent prognostic factor of distant metastasis development in breast cancer.

Cited by 10 publications

References 52 publications

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

MicroRNA‐125b as a tumor suppressor by targeting MMP11 in breast cancer

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