Evaluation of the clinical utility of kallikrein-related peptidase 6 gene (KLK6) downregulation in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10606-10606 ◽  
Author(s):  
Kleita Michaelidou ◽  
Alexandros Tzovaras ◽  
Nikolaos Tsoukalas ◽  
Konstantinos Mavridis ◽  
Grecory Tsoukalas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Breast Tissue ◽  
Public Health Problem ◽  
Breast Tumors ◽  
Tumor Stage ◽  
Cancer Biomarker ◽  
Negative Association ◽  
Mrna Levels ◽  
Female Population

10606 Background: Breast cancer (BC), the most common malignancy among the female population, remains a crucial public health problem. The identification and exploitation of novel molecular biomarkers can contribute in the multidimensional approach which is required for optimal management of BC patients. The abnormal expression of several KLK members has been documented for breast cancer. Interestingly, many of these genes are found to be potential prognostic markers for this malignancy. KLK6 expression is positively associated with tumor progression in various human malignancies; however in breast cancer, it can restrain tumor progression. We therefore sought to investigate the possible clinical value of KLK6 as a breast cancer biomarker. Methods: Total RNA was isolated from 107 breast tumors and their matched normal compartments. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. Quantitative Real-time PCR was performed, for KLK6 mRNA quantification, using the SYBR Green chemistry. Relative quantification analysis was made using the comparative Ct (2-ΔΔCT) method. HPRT1 was used as an endogenous control gene and BT-474 breast cancer cell line served as a calibrator. Results: KLK6 mRNA levels were significantly downregulated in the cancerous breast tissue specimens compared to their normal counterparts (p<0.001). Additionally, a negative association was observed between KLK6 expression status and tumor stage, given the fact that 54.2% of less advanced breast tumors (TNM stage≤ T2a) were KLK6-positive compared to the 34.6% of more advanced-stage tumors (TNM >T2a) (p=0.034). Moreover, a statistically significant negative correlation was documented between KLK6 mRNA levels and estrogen (p<0.001) and progesterone receptor (p=0.003) statuses. Conclusions: The downregulation of KLK6 in cancerous compared to normal sections of breast tissue samples reflects the reported tumor suppressor properties of KLK6 gene in breast malignancies. Furthermore, the negative association of KLK6 mRNA expression with tumor stage, ER and PR statuses reveals the putative role of KLK6 as a promising prognostic breast cancer biomarker.

Case of second primary breast cancer in ectopic breast tissue and review of the literature

2021 ◽  
Vol 14 (4) ◽  
pp. e241361
Author(s):  
Jamin Kweku Addae ◽  
Thomas Genuit ◽  
Joseph Colletta ◽  
Kathy Schilling
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Breast Tissue ◽  
Delayed Diagnosis ◽  
Left Breast ◽  
Second Primary ◽  
Female Population ◽  
Accessory Breast ◽  
History Of ◽  
High Index Of Suspicion

Accessory breast tissue (ABT) is found in approximately 2%–6% of the female population and are subject to most of the physiological and pathological changes that occur in pectoral breast. Primary breast cancer occurring in ABT is a rare occurrence and a second primary breast cancer occurring in an accessory breast has never been reported. We report the case of a 60-year-old woman with a history of mastectomy for left breast cancer 5 years prior to presentation, who presented with an enlarging right axilla mass found to be a second primary breast cancer in an accessory tissue on biopsy. Many physicians are unfamiliar with the clinical presentation of accessory breast cancer due to the rarity of the condition and this ultimately results in delayed diagnosis and advanced disease at presentation. It is therefore prudent that physicians have a high index of suspicion when patients present with axillary masses.

scholarly journals Clinical value of peripheral blood M2/M1 like monocyte ratio in the diagnosis of breast cancer and the differentiation between benign and malignant breast tumors

2019 ◽  
Author(s):  
Mustafa Fadhil ◽  
Omar Abdul- Rasheed ◽  
Manwar Al-Naqqash
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Breast Tumor ◽  
Healthy Subjects ◽  
Breast Tumors ◽  
Breast Cancer Patients ◽  
Cancer Tumor ◽  
Malignant Breast

Background: During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. In response to multiple microenvironmental signals from the tumor and stromal cells, macrophages change their functional phenotypes. Based on their function, macrophages are commonly classified into both, classical M1 and alternative M2 macrophages. M2-like tumor-associated macrophages promote breast tumor growth and survival, and may migrate into the peripheral blood. However, the level of circulating M2/M1-like monocyte ratio in the peripheral blood of breast cancer patients has not been yet clarified. Aim: To compare peripheral blood M2/M1 monocyte ratio among breast cancer patients, benign breast tumor patients and healthy subjects. Also, to investigate the role of peripheral blood M2/M1 monocyte ratio as a circulating breast cancer tumor marker and to asses the validity of this marker in differentiation between benign and malignant breast tumors. Methods: Flow cytometry technique was used to determine the peripheral blood M2/M1 monocyte ratio in three groups of subjects, i.e. 45 patients with breast cancer, 40 patients with benign breast tumor, and 40 healthy subjects as a control group. The results of carbohydrate antigen15-3 (CA15-3) determination were analyzed comparatively. Results: The peripheral blood M2/M1 monocyte ratio in patients with breast cancer (0.27±0.1) was significantly higher (P<0.001) than that in healthy subjects (0.07±0.05) and than in benign tumor subjects (0.08±0.04). The area under the receiver operating characteristic (ROC) curve of peripheral blood M2/M1 monocyte ratio determination was significantly higher (P≤0.001) than that of CA15-3 levels. Conclusion: M2/M1-like monocyte ratio is of a high diagnostic value for breast cancer and is a promising differentiating marker between benign and breast cancer tumor groups.

scholarly journals Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1188
Author(s):  
Yanjun Zhou ◽  
Jonas S. Heitmann ◽  
Korbinian N. Kropp ◽  
Martina Hinterleitner ◽  
André Koch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Platelet Activation ◽  
Tumor Stage ◽  
Breast Cancer Patients ◽  
Healthy Individuals ◽  
Healthy Donors ◽  
A Disintegrin And Metalloproteinase ◽  
Further Development

Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. Here, we report that platelet-derived ADAM17 (pADAM17) is regulated upon platelet activation of breast cancer patients, but not of healthy individuals. The observed downregulation of pADAM17 on platelets of cancer patients correlated with clinical parameters related to tumor progression including tumor stage and the occurrence of metastasis. Our data identify an association between platelet activation, modulation of platelet-derived ADAM17, and metastasis. In conclusion, we demonstrate that further development of pADAM17 as a liquid biomarker is warranted for monitoring disease progression in breast cancer.

scholarly journals Quantifying Breast Cancer-Driven Fiber Alignment and Collagen Deposition in Primary Human Breast Tissue

2021 ◽  
Vol 9 ◽  
Author(s):  
Rakesh Gurrala ◽  
C. Ethan Byrne ◽  
Loren M. Brown ◽  
Rafael Felix P. Tiongco ◽  
Margarite D. Matossian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Tissue ◽  
Breast Tumors ◽  
Collagen Deposition ◽  
Human Breast ◽  
Human Breast Tissue ◽  
Fiber Alignment ◽  
Primary Human Breast

Solid tumor progression is significantly influenced by interactions between cancer cells and the surrounding extracellular matrix (ECM). Specifically, the cancer cell-driven changes to ECM fiber alignment and collagen deposition impact tumor growth and metastasis. Current methods of quantifying these processes are incomplete, require simple or artificial matrixes, rely on uncommon imaging techniques, preclude the use of biological and technical replicates, require destruction of the tissue, or are prone to segmentation errors. We present a set of methodological solutions to these shortcomings that were developed to quantify these processes in cultured, ex vivo human breast tissue under the influence of breast cancer cells and allow for the study of ECM in primary breast tumors. Herein, we describe a method of quantifying fiber alignment that can analyze complex native ECM from scanning electron micrographs that does not preclude the use of replicates and a high-throughput mechanism of quantifying collagen content that is non-destructive. The use of these methods accurately recapitulated cancer cell-driven changes in fiber alignment and collagen deposition observed by visual inspection. Additionally, these methods successfully identified increased fiber alignment in primary human breast tumors when compared to human breast tissue and increased collagen deposition in lobular breast cancer when compared to ductal breast cancer. The successful quantification of fiber alignment and collagen deposition using these methods encourages their use for future studies of ECM dysregulation in human solid tumors.

scholarly journals Platelet-expressed immune checkpoint regulator GITRL in breast cancer

2021 ◽  
Author(s):  
Yanjun Zhou ◽  
Jonas S. Heitmann ◽  
Kim L. Clar ◽  
Korbinian N. Kropp ◽  
Martina Hinterleitner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Tumor Stage ◽  
Breast Cancer Patients ◽  
Effector Functions ◽  
Checkpoint Molecule ◽  
Cellular Context ◽  
Inhibitory Immune Checkpoint

AbstractOwing to their key role in several diseases including cancer, activating and inhibitory immune checkpoint molecules are increasingly exploited as targets for immunotherapy. Recently, we demonstrated that platelets, which largely influence tumor progression and immune evasion, functionally express the ligand of the checkpoint molecule GITR. This immunoreceptor modulates effector functions of T cells and NK cells with its function varying dependent on cellular context and activation state. Here, we provide a comparative analysis of platelet-derived GITRL (pGITRL) in breast cancer patients and healthy volunteers. The levels of pGITRL were found to be higher on platelets derived from cancer patients and appeared to be specifically regulated during tumor progression as exemplified by several clinical parameters including tumor stage/grade, the occurrence of metastases and tumor proliferation (Ki67) index. In addition, we report that pGITRL is upregulated during platelet maturation and particularly induced upon exposure to tumor-derived soluble factors. Our data indicate that platelets modulate the GITR/GITRL immune checkpoint in the context of malignant disease and provide a rationale to further study the GITR/GITRL axis for exploitation for immunotherapeutic intervention in cancer patients.

scholarly journals NLRC4, ASC and Caspase-1 Are Inflammasome Components That Are Mediated by P2Y2R Activation in Breast Cancer Cells

2020 ◽  
Vol 21 (9) ◽  
pp. 3337 ◽  
Author(s):  
Hana Jin ◽  
Hye Jung Kim
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Protein Levels ◽  
Caspase 1 ◽  
Tnf Α

The inflammasomes are reported to be associated with tumor progression. In our previous study, we determined that extracellular ATP enhances invasion and tumor growth by inducing inflammasome activation in a P2Y purinergic receptor 2 (P2Y2R)-dependent manner. However, it is not clear which inflammasome among the diverse complexes is associated with P2Y2R activation in breast cancer. Thus, in this study, we determined which inflammasome components are regulated by P2Y2R activation and are involved in tumor progression in breast cancer cells and radiotherapy-resistant (RT-R)-breast cancer cells. First, we found that NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3); NLR family caspase activation and recruitment domain (CARD) containing 4 (NLRC4); apoptosis-associated speck-like protein containing a CARD complex (ASC); and caspase-1 mRNA levels were upregulated in RT-R-MDA-MB-231 cells compared to MDA-MB-231 cells, whereas tumor necrosis factor-α (TNF-α) or ATP treatment induced NLRC4, ASC, and caspase-1 but not NLRP3 protein levels. Moreover, TNF-α or ATP increased protein levels of NLRC4, ASC, and caspase-1 in a P2Y2R-dependent manner in MDA-MB-231 and RT-R-MDA-MB-231 cells. In addition, P2Y2R activation by ATP induced the secretion of IL-1β and VEGF-A, as well as invasion, in MDA-MB-231 and RT-R-MDA-MB-231 cells, which was inhibited by NLRC4, ASC, and caspase-1 small interfering RNA (siRNA). Taken together, this report suggests that P2Y2R activation by ATP induces tumor invasion and angiogenesis through inflammasome activation, specifically by regulating the inflammasome components NLRC4, ASC, and caspase-1.

scholarly journals Detection of Hypermethylation BRCA1/2 Gene Promotor in Breast Tumors Among Moroccan Women

2021 ◽  
Author(s):  
Imane Saif ◽  
Amal Bouziyane ◽  
Mustapha Benhessou ◽  
Mohamed El karroumi ◽  
Moulay Mustapha Ennaji
Keyword(s):  
Breast Cancer ◽  
Gene Expression Regulation ◽  
Cell Cancer ◽  
Breast Tumors ◽  
Tumor Stage ◽  
Epigenetic Factor ◽  
Promoter Gene ◽  
Gene Promotor ◽  
Moroccan Women ◽  
The Impact

Abstract Background: The promoter region is a key element of gene expression regulation. In mammals, most of the genes present, at the level of their promoter, a large number of islands CpG. Age is seen as another factor promoting breast cell cancer and the tumor stage. Aim: this study aimed to explore the hypermethylation of the BRCA1/2 promoter gene in breast cancer women and correlation with age and tumor stage.Materials and methods: fifty biopsies were derived from Moroccan women treated for breast carcinoma, the DNA extracted was treated by bisulphite and the targeted BRCA1/2 Amplicons were amplified by specific methylation primers (MSP). Results: the result shows that 62% of the samples were BRCA1 methylated in addition and negative result for BRCA2, these positive epigenetic factor were remarkable in women over 47 years and at the stage of malignant tumor.Conclusion: these results show that half of the methylated samples are positive and the majority are over 47 years old, and confirms the impact of age on methylation and might be other factor of breast cancer development.

scholarly journals Single-Cell RNA Sequencing of a Postmenopausal Normal Breast Tissue Identifies Multiple Cell Types That Contribute to Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3639
Author(s):  
Sen Peng ◽  
Lora L. Hebert ◽  
Jennifer M. Eschbacher ◽  
Suwon Kim
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Rna Sequencing ◽  
Breast Tissue ◽  
Breast Tumors ◽  
Cell Types ◽  
Cell Cluster ◽  
Cell Type ◽  
Cell Clusters ◽  
Cluster 2

The human breast is composed of diverse cell types. Studies have delineated mammary epithelial cells, but the other cell types in the breast have scarcely been characterized. In order to gain insight into the cellular composition of the tissue, we performed droplet-mediated RNA sequencing of 3193 single cells isolated from a postmenopausal breast tissue without enriching for epithelial cells. Unbiased clustering analysis identified 10 distinct cell clusters, seven of which were nonepithelial devoid of cytokeratin expression. The remaining three cell clusters expressed cytokeratins (CKs), representing breast epithelial cells; Cluster 2 and Cluster 7 cells expressed luminal and basal CKs, respectively, whereas Cluster 9 cells expressed both luminal and basal CKs, as well as other CKs of unknown specificity. To assess which cell type(s) potentially contributes to breast cancer, we used the differential gene expression signature of each cell cluster to derive gene set variation analysis (GSVA) scores and classified breast tumors in The Cancer Gene Atlas (TGGA) dataset (n = 1100) by assigning the highest GSVA scoring cell cluster number for each tumor. The results showed that five clusters (Clusters 2, 3, 7, 8, and 9) could categorize >85% of breast tumors collectively. Notably, Cluster 2 (luminal epithelial) and Cluster 3 (fibroblast) tumors were equally prevalent in the luminal breast cancer subtypes, whereas Cluster 7 (basal epithelial) and Cluster 9 (other epithelial) tumors were present primarily in the triple-negative breast cancer (TNBC) subtype. Cluster 8 (immune) tumors were present in all subtypes, indicating that immune cells may contribute to breast cancer regardless of the subtypes. Cluster 9 tumors were significantly associated with poor patient survival in TNBC, suggesting that this epithelial cell type may give rise to an aggressive TNBC subset.

High tumoral levels of Kiss1 and G-protein-coupled receptor 54 expression are correlated with poor prognosis of estrogen receptor-positive breast tumors

2007 ◽  
Vol 14 (3) ◽  
pp. 691-702 ◽  
Author(s):  
Didier Marot ◽  
Ivan Bieche ◽  
Chantal Aumas ◽  
Stéphanie Esselin ◽  
Céline Bouquet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
G Protein ◽  
Breast Tumors ◽  
Metastasis Suppressor ◽  
Mrna Levels ◽  
Breast Cancers ◽  
G Protein Coupled Receptor ◽  
Primary Tumors ◽  
G Protein Coupled

KiSS1 is a putative metastasis suppressor gene in melanoma and breast cancer-encoding kisspeptins, which are also described as neuroendocrine regulators of the gonadotropic axis. Negative as well as positive regulation of KiSS1 gene expression by estradiol (E2) has been reported in the hypothalamus. Estrogen receptor α (ERα level is recognized as a marker of breast cancer, raising the question of whether expression of KiSS1 and its G-protein-coupled receptor (GPR54) is down- or upregulated by estrogens in breast cancer cells. KiSS1 was found to be expressed in MDA-MB-231, MCF7, and T47D cell lines, but not in ZR75-1, L56Br, and MDA-MB-435 cells. KiSS1 mRNA levels decreased significantly in ERα-negative MDA-MB-231 cells expressing recombinant ERα. In contrast, tamoxifen (TAM) treatment of ERα-positive MCF7 and T47D cells increased KiSS1 and GPR54 levels. The clinical relevance of this negative regulation of KiSS1 and GPR54 by E2 was then studied in postmenopausal breast cancers. KiSS1 mRNA increased with the grade of the breast tumors. ERα-positive invasive primary tumors expressed sevenfold lower KiSS1 levels than ERα-negative tumors. Among ERα-positive breast tumors from postmenopausal women treated with TAM, high KiSS1 combined with high GPR54 mRNA tumoral levels was unexpectedly associated with shorter relapse-free survival (RFS) relative to tumors expressing low tumoral mRNA levels of both genes. The contradictory observation of putative metastasis inhibitor role of kisspeptins and RFS to TAM treatment suggests that evaluation of KiSS1 and its receptor tumoral mRNA levels could be new interesting markers of the tumoral resistance to anti-estrogen treatment.

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