Adhesion molecules in breast carcinoma: a challenge to the pathologist

Rossetti, Claudia; Reis, Beatriz da Costa Aguiar Alves; Delgado, Pamela de Oliveira; Azzalis, Ligia Ajaime; Junqueira, Virgínia Berlanga Campos; Feder, David; Fonseca, Fernando L. A.

doi:10.1590/1806-9282.61.01.081

Cited by 5 publications

(6 citation statements)

References 27 publications

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“…The role of this pathway has been recognized in the carcinogenesis and metastasis of breast cancer. Therefore, evaluation of the involved genes can be diagnostic, prognostic and therapeutic targets 22,56 . Besides, the regulatory role of GATA3 in adhesion molecules expression has been identified in cell culture analysis 57 .…”

Section: Discussionmentioning

confidence: 99%

“…To gain an insight into the functionality of the DEGs between normal and tumor (mutant and non-mutant) samples, gene set enrichment analysis was performed using the Metascape and DAVID functional enrichment tool. According to DAVID outputs, 36 pathways found to be significantly different between GATA3-mutant and normal samples, 7 pathways had been previously reported as the most important pathways related to breast cancer (p ≤ 0.05) [20][21][22] . Evaluation of www.nature.com/scientificreports/ non-mutant tumors against normal tissue samples indicated 37 significantly different.…”

Section: Functional Annotation Analysis Of Differentially Expressed Genesmentioning

confidence: 99%

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GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Afzaljavan

Sadr

Savas

et al. 2021

Sci Rep

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The effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein–protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.

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Section: Discussionmentioning

confidence: 99%

Section: Functional Annotation Analysis Of Differentially Expressed Genesmentioning

confidence: 99%

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Afzaljavan

Sadr

Savas

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The formation of spheroids by many BC cell lines is also known to depend on the expression of E-cadherin ( Iglesias et al, 2013 ). At the same time, the level of E-cadherin expression in tumor tissue is significantly associated with the prognosis of many types of cancer, including BC (low level is associated with a poor prognosis) ( Rossetti et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…What is more, the expression of many adhesion molecules that can potentially participate in the formation of intercellular contacts in spheroids is associated with the prognosis of the disease. In particular, low expression of claudin (one of the structural components of tight junctions) in BC cells is associated with a poor prognosis ( Rossetti et al, 2015 ). Thus, the study of intercellular adhesion can be useful in assessing the metastatic potential of cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Expression of ELOVL5 and IGFBP6 Genes on the Metastatic Potential of Breast Cancer Cells

et al. 2021

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Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of ELOVL5 and IGFBP6 genes is associated with a higher risk of the formation of distant metastases in BC. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of BC cells as a result of the stable knockdown of ELOVL5 and IGFBP6 genes. The knockdown of ELOVL5 and IGFBP6 genes was found to lead to a strong increase in the expression of the matrix metalloproteinase (MMP) MMP1. These results were in good agreement with the correlation analysis of gene expression in tumor samples from patients and were additionally confirmed by zymography. The knockdown of ELOVL5 and IGFBP6 genes was also discovered to change the expression of a group of genes involved in the formation of intercellular contacts. In particular, the expression of the CDH11 gene was markedly reduced, which also complies with the correlation analysis. The spheroid formation assay showed that intercellular adhesion decreased as a result of the knockdown of the ELOVL5 and IGFBP6 genes. Thus, the obtained data indicate that malignant breast tumors with reduced expression of the ELOVL5 and IGFBP6 genes can metastasize with a higher probability due to a more efficient invasion of tumor cells.

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“…Similarly, MMP-9 plays an important role in migration and survival, and speeds up the disease progression of chronic lymphocytic leukemias (CLL) [11]. MMP-2, MMP-9 and MMP-13 are also reported to be overexpressed in breast cancer patients and correlated with more aggressive phenotypes of breast cancer, poor prognosis and decreased life expectancy [49,138,141]. Cathepsin B has been reported to be highly expressed in breast cancer patients and mainly responsible for degrading collagen, fibronectin, laminin and proteoglycans, thereby promoting nodal metastasis [48,120,158].…”

Section: Disease-specific Proteases Locally Unlock and Reactivate Pro-antibodies In The Disease Regionmentioning

confidence: 99%

Ab locks for improving the selectivity and safety of antibody drugs

Lin

Chuang

et al. 2020

J Biomed Sci

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Monoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neutralization by mAbs may cause severe adverse events. Improving the selectivity of mAbs to distinguish target antigens at the disease site from normal healthy tissue and reducing severe adverse events caused by the mechanisms-of-action of mAbs is still a pressing need. Development of pro-antibodies (pro-Abs) by installing a protease-cleavable Ab lock is a novel and advanced recombinant Ab-based strategy that efficiently masks the antigen binding ability of mAbs in the normal state and selectively “turns on” the mAb activity when the pro-Ab reaches the proteolytic protease-overexpressed diseased tissue. In this review, we discuss the design and advantages/disadvantages of different Ab lock strategies, focusing particularly on spatial-hindrance-based and affinity peptide-based approaches. We expect that the development of different masking strategies for mAbs will benefit the local reactivity of mAbs at the disease site, increase the therapeutic efficacy and safety of long-term treatment with mAbs in chronic diseases and even permit scientists to develop Ab drugs for formerly undruggable targets and satisfy the unmet medical needs of mAb therapy.

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Adhesion molecules in breast carcinoma: a challenge to the pathologist

Cited by 5 publications

References 27 publications

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Effect of the Expression of ELOVL5 and IGFBP6 Genes on the Metastatic Potential of Breast Cancer Cells

Ab locks for improving the selectivity and safety of antibody drugs

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