scholarly journals High nerve density in breast cancer is associated with poor patient outcome

2021 ◽  
Author(s):  
Dong Li ◽  
Li Na Hu ◽  
Ting La ◽  
Li Yuan Wei ◽  
Xiao Jun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nervous System ◽  
Nerve Trunk ◽  
Clinicopathological Parameters ◽  
Specific Marker ◽  
Breast Cancers ◽  
Human Breast ◽  
Nerve Fibres ◽  
Cancer Pathogenesis ◽  
Poor Patient

Abstract Background: Active crosstalk between the nervous system and breast cancer cells as well as other cell types within the tumour microenvironment has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to better define the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features.Methods: Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 (PGP9.5) and growth-associated protein 43 (GAP-43), and the sympathetic nerve-specific marker tyrosine hydroxylase (TH). Nerve trunks (comprised of many nerve fibres/axons) and isolated nerve fibres (positively stained cells with or without typical morphology of axons outside definable nerve trunks) were quantitated. The chi-squared test was used to determine the associations between nerve trunk or isolated nerve fibre counts and clinicopathological parameters. The Log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). A multivariate analysis was performed according to the Cox Proportional Hazards Model to assess independent prognostic factors.Results: Nerve trunks and isolated nerve fibres were detected in 75% and 77% of breast cancers, respectively. The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin (positive for TH). While high density of nerve trunks or isolated nerve fibres was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Conclusions: Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.

scholarly journals MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 942
Author(s):  
Mei Qi Kwa ◽  
Rafael Brandao ◽  
Trong H. Phung ◽  
Jianfeng Ge ◽  
Giuseppe Scieri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression Signature ◽  
Genomic Analysis ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Human Breast ◽  
Breast Cancer Development

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

The Pattern of Proline, Glutamic Acid, and Leucine-Rich Protein 1 Expression in Chinese Women with Primary Breast Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Primary Breast Cancer ◽  
Chinese Women ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Her 2

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

scholarly journals Extracellular Calcium-Sensing Receptor Expression and Its Potential Role in Regulating Parathyroid Hormone-Related Peptide Secretion in Human Breast Cancer Cell Lines*

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4357-4364 ◽  
Author(s):  
Jennifer L. Sanders ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Toru Yamaguchi ◽  
Robert R. Butters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Breast

Abstract Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-β (TGFβ), which is released from resorbed bone. Elevated extracellular calcium (Cao2+) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Cao2+-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Cao2+ and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGFβ1 (0.2, 1, or 5 ng/ml) augmented both basal and high Cao2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Cao2+ and TGFβ within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.

scholarly journals XIV.—On the Relation of Nerves to Odontoblasts, and on the Growth of Dentine

1892 ◽  
Vol 36 (2) ◽  
pp. 321-333 ◽  
Author(s):  
W. G. Aitchison Robertson
Keyword(s):  
Nervous System ◽  
Nerve Trunk ◽  
The Body ◽  
Osmic Acid ◽  
Nerve Fibres ◽  
Incisor Tooth ◽  
Highly Sensitive ◽  
Single Nerve ◽  
Lateral Branches ◽  
External Stimuli

Clinical and pathological observation both show that the dentine of the tooth is very closely connected with the nervous system, and is in consequence highly sensitive. Upon what structures does the sensibility of the dentine depend? In what manner is the dentine connected with the nerves of the pulp so as to become so sensitive to external stimuli?Perhaps there is no other structure in the body which is so largely supplied with nerves as the pulp of the tooth; even in the smallest fragment we find many nerve fibres. If we take the pulp from the incisor tooth of an ox and examine it after having allowed it to lie in a solution of osmic acid for a few minutes, we can see clearly through the darkened semi-transparent tissue a large blackened nerve trunk passing up the centre of the pulp, giving off on its way innumerable lateral branches, and dividing in a brush-like manner near the upper part of the pulp. All the fine branches are directed towards the periphery of the pulp. In longitudinal sections of the pulp we can see the same in greater detail; many large bundles of medullated and non-medullated nerve fibres running longitudinally near the centre and giving off lateral branches, which are found in great numbers near the periphery and divide into single nerve fibres just under the odontoblastic layer, being specially numerous at the apex of the pulp.

scholarly journals Characterization of organoid cultured human breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Nadine Goldhammer ◽  
Jiyoung Kim ◽  
Vera Timmermans-Wielenga ◽  
Ole William Petersen
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Human Breast Cancer ◽  
Breast Cancers ◽  
Basal Cells ◽  
Human Breast ◽  
Contemporary Culture ◽  
Mucin 1 ◽  
Organoid Cultures ◽  
Primary Human Breast

AbstractOrganoid cultures are increasingly used to model human cancers experimentally with a view to tailoring personalized medicine and predicting drug responses. Breast cancer is no exception, but in particular, primary breast cancer poses some inherent difficulties due to the frequent presence of residual non-malignant cells in the biopsies. We originally developed an assay for the distinction between malignant and non-malignant structures in primary breast cancer organoid cultures (Petersen et al., Proc Natl Acad Sci (USA) 89(19):9064–8, 1992). Here, we apply this assay to assess the frequency of normal-like organoids in primary breast carcinoma cultures and the cellular composition as a consequence of passaging. We find that in consecutively collected samples of primary human breast cancers, residual non-malignant tissues were observed histologically in five out of ten biopsies. Based on relevant morphogenesis and correct polarization as recorded by expression in luminal epithelial cells of mucin 1 (Muc1), occludin, and keratin 19 (K19) and expression in basal cells of integrin β4, p63, and K14, non-malignant organoids were present in all primary human breast cancer-derived cultures. Furthermore, passaging in a contemporary culture medium was in favor of the selective expansion of basal-like cells. We conclude that organoid cultures of human breast cancers are most representative of the tissue origin in primary culture.

Immunohistochemical Study of Ten Cases of Argyrophilic Carcinoma (Carcinoid) of the Breast

1988 ◽  
Vol 74 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Salvatore Andreola ◽  
Emanuela Di Re ◽  
Mirella Merson ◽  
Lorenza Maggiulli ◽  
Patrizia De Palma
Keyword(s):  
Breast Cancer ◽  
Natural History ◽  
Human Breast Cancer ◽  
Immunohistochemical Study ◽  
Secretory Activity ◽  
Controversial Issue ◽  
Breast Cancers ◽  
Human Breast ◽  
History Of

The significance of argyrophilia in human breast cancer is still a controversial issue. We tested immunohistochemically 10 cases of argyrophilic carcinomas of the breast and found evidence of immunoreactivity with neuroendocrine markers: chromogranin, NSE, gastrin, insulin and bombesin. Argyrophilia was demonstrated in breast cancers of the usual types and was found to be related to the secretory activity of neoplastic cells. Unfortunately, no adequate follow-up data are available to clarify the natural history of argyrophilic breast cancer. A clinical treatment different from that of conventional breast cancer is not at present justified.

scholarly journals Somatic Mutation of PIK3CA (H1047R) Is a Common Driver Mutation Hotspot in Canine Mammary Tumors as Well as Human Breast Cancers

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2006 ◽  
Author(s):  
Kang-Hoon Lee ◽  
Hyeon-Ji Hwang ◽  
Hyun Ji Noh ◽  
Tae-Jin Shin ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Human Cancer ◽  
Association Studies ◽  
Cell Metabolism ◽  
Driver Mutations ◽  
Genome Wide Association Studies ◽  
Breast Cancers ◽  
Human Breast ◽  
Normal Tissues ◽  
Whole Exome

Breast cancer is one of the most frequently diagnosed cancers in both women and female dogs. Genome-wide association studies in human breast cancer (HBC) have identified hundreds of genetic variations and somatic driver mutations. However, only a handful of variants have been studied for rare HBC and their associations remain inconclusive. Spontaneous canine mammary tumor (CMT) is a great model for HBC, with clinical similarity. We thus performed whole-exome sequencing in 20 pairs of CMT and normal tissues in dogs. We newly found that PIK3CA was the most frequently mutated gene in CMT (45%). Furthermore, canine PIK3CA A3140G (H1047R), at what is known as the mutational hotspot of HBC, is also a hotspot in CMT. Targeted sequencing confirmed that 29% of CMTs had the same PIK3CA A3140G mutation. Integration of the transcriptome suggests that the PIK3CA (H1047R) induced cell metabolism and cell cycle via an increase of PCK2 and a decrease of CDKN1B but had no effect on cell apoptosis. We identified additional significantly mutated genes, including SCRN1 and CLHC1, which have not been reported in HBC. Our study recapitulated some known HBC-associated genes and human cancer signatures in CMT, and identified novel genes that may be relevant to HBC. This study may allow us to better understand both HBC and CMT and lend new insights into the development of biomarkers.

A novel therapeutic strategy for ER-negative human breast cancers, targeting AP-1 activity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14129-14129
Author(s):  
K. Sakaguchi ◽  
H. Nakajima ◽  
I. Fujiwara ◽  
N. Mizuta ◽  
J. Magae
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancers ◽  
Human Breast ◽  
Er Positive

14129 Background: While agents targeting estrogen receptors are the most effective in adjuvant therapy for human breast cancers expressing estrogen receptor(ER), breast cancers lacking ER are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Although a transcription factor, AP-1, is known to be related to tumor malignancy including metastasis, invasion and drug-resistance, it remains to be elucidated how AP-1 plays in development and expression of malignant characters of human breast cancers. Methods and Results: Here, we used MX-1, a human breast cancer cell line lacking ER and several ER positive cell lines, to clarify the roles of AP-1 and the therapeutic efficacy of ascochlorin, a newly developed prenylphenol antibiotic on ER-negative breast cancer. We found that MX-1 exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos and Fra-1 when compared with conventional ER-positive human breast cancer cell lines. Consistent with this study in vitro, histological study on human breast cancer tissues suggests that ER-negative cancers express high Fra-1 protein, and that paclitaxel- sensitive cancers express low Fra-1 protein. The ascochlorin, which inhibits AP-1 through the Erk signaling pathway, suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Moreover, administration of ascochlorin elongated life span of mice intraperitoneally implanted with murine mammary carcinoma cells. Conclusions: Our results suggest that AP-1 is an effective clinical target molecule for the treatment of ER-negative human breast cancer, and that ascochlorin is promising therapeutic agent for these refractory breast cancers. No significant financial relationships to disclose.

scholarly journals Mast cells in luminal vs non-luminal breast cancers

2021 ◽  
Vol 64 (4) ◽  
pp. 35-38
Author(s):  
Ecaterina Carpenco ◽  
◽  
Veaceslav Fulga ◽  
Valeriu David ◽  
Ecaterina Foca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mast Cells ◽  
Immune Cells ◽  
Hormone Receptors ◽  
Molecular Profile ◽  
Specific Marker ◽  
Breast Cancers ◽  
Her2 Expression ◽  
Breast Carcinomas ◽  
Mast Cell Tryptase

Background: Tumor growth and development is determined by the mutual interaction between the cancer cells themselves and the microenvironment. It contains various elements, including immune cells. Of all, mast cells have one of the most controversial roles. The aim of the present study was to evaluate the expression of mast cell tryptase in the luminal and non-luminal subtypes of breast cancer and establish a possible link between infiltration with MCs and expression of hormone receptors. Material and methods: The experimental study included 80 cases of breast carcinomas that were analyzed immunohistochemically in order to establish the molecular profile and the expression of tryptase, a specific marker of mast cells. The data were processed using the SPSS program. Pearson’s coefficient (r) and the other values were considered statistically significant in case of p≤0.05. Results: Both intratumoral mast cells (MCit) and peritumoral mast cells (MCpt) correlated with the expression of hormone receptors for estrogen (ER) and progesterone (PR). Thus, the following relations were established: MCit and ER (r=0.343, p=0.002), MCpt and ER (r=0.394, p=0.000295) and MCpt and PR (r=0.386, p=0.000409). Statistically significant correlations between HER2 expression and mast cells content have not been established. Conclusions: Mast cells invasion, peri- and intratumoral, is strongly influenced by the expression of hormone receptors. The luminal subtypes of breast cancer are characterized by a higher density of mast cells.

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