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Heterogeneity breast metastasis

Maria Rosaria Ruocco, Angelica Avagliano, Giuseppina Granato, Valeria Imparato, Stefania Masone, Mariorosario Masullo, Rosarita Nasso, Stefania Montagnani, Alessandro Arcucci
Breast cancer is the most common cancer in women, which incidence has increased in recent years. It is constituted by very heterogeneous tissue characterized by an abnormal microenvironment regulating tumor progression and providing evasion from cancer therapies. Breast cancer associated fibroblasts (BCAFs) are the main cell type of breast cancer microenvironment and can represent up to 80 % of the tumor mass. In particular, BCAFs induce cancer initiation, proliferation, invasion and metastasis by undergoing an irreversible activation process associated with secretion of growth factors, cytokines, and paracrine interactions...
March 9, 2018: Current Medicinal Chemistry
Christiana Neophytou, Panagiotis Boutsikos, Panagiotis Papageorgis
Breast cancer represents a highly heterogeneous disease comprised by several subtypes with distinct histological features, underlying molecular etiology and clinical behaviors. It is widely accepted that triple-negative breast cancer (TNBC) is one of the most aggressive subtypes, often associated with poor patient outcome due to the development of metastases in secondary organs, such as the lungs, brain, and bone. The molecular complexity of the metastatic process in combination with the lack of effective targeted therapies for TNBC metastasis have fostered significant research efforts during the past few years to identify molecular "drivers" of this lethal cascade...
2018: Frontiers in Oncology
Reza Dayer, Sadegh Babashah, Shirin Jamshidi, Majid Sadeghizadeh
Objective: Breast cancer is considered as a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. The CXC chemokine receptor 4 (CXCR4) expression was found to be correlated with poor overall survival in invasive breast carcinoma patients. Here, we sought to investigate the expression levels of the CXCR4-CXC chemokine ligand 12 (CXCL12) chemokine axis and their association with clinicopathologic features and lymph node metastasis in invasive breast carcinoma...
January 2018: Journal of Cancer Research and Therapeutics
I V Deryusheva, M Tsyganov, E Y Garbukov, M K Ibragimova, Ju G Kzhyshkovska, E Slonimskaya, N V Cherdyntseva, N V Litviakov
One of the factors providing the diversity and heterogeneity of malignant tumors, particularly breast cancer, are genetic variations, due to gene polymorphism, and, especially, the phenomenon of loss of heterozygosity (LOH). It has been shown that LOH in some genes could be a good prognostic marker. AIM: To perform genome-wide study on LOH in association with metastasis-free survival in breast cancer. MATERIALS AND METHODS: The study involved 68 patients with breast cancer...
July 2017: Experimental Oncology
Marni B Siegel, Xiaping He, Katherine A Hoadley, Alan Hoyle, Julia B Pearce, Amy L Garrett, Sunil Kumar, Vincent J Moylan, Claudia M Brady, Amanda Ed Van Swearingen, David Marron, Gaorav P Gupta, Leigh B Thorne, Niamh Kieran, Chad Livasy, Elaine R Mardis, Joel S Parker, Mengjie Chen, Carey K Anders, Lisa A Carey, Charles M Perou
Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading...
February 26, 2018: Journal of Clinical Investigation
Qingshuo Meng, Jia Meng, Wei Ran, Junyang Wang, Yihui Zhai, Pengcheng Zhang, Yaping Li
Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal-like cells at their core and fast proliferating cells on the periphery. It is desirable and beneficial to treat TNBC cells of different phenotypes with the most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally specific activity when irradiated by light. Under conditions mimicking superficial tumor tissue with sufficient light input, TNBC cells are mainly killed by the photodynamic therapy (PDT) function of CDTNs...
February 22, 2018: ACS Nano
Divya Nagarajan, Stephanie E B McArdle
Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified-Luminal-A, Luminal-B, HER2⁺, Triple negative/basal like (TNBC) and normal like-subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen receptor, immuno-modulatory and unstable). Although genetic and epigenetic changes are key pathogenic events, the immune system plays a substantial role in promoting progression and metastasis...
February 11, 2018: Biomedicines
Jiaqing Hao, Fei Yan, Yuwen Zhang, Ashley Triplett, Ying Zhang, Debra A Schultz, Yanwen Sun, Jun Zeng, Kevin A T Silverstein, Qi Zheng, David A Bernlohr, Margot P Cleary, Nejat K Egilmez, Edward Sauter, Shujun Liu, Jill Suttles, Bing Li
Tumor associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically-relevant markers for pro-tumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid binding protein (A-FABP) in TAM promotes breast cancer progression. While upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis...
February 6, 2018: Cancer Research
Una Kjällquist, Rikard Erlandsson, Nicholas P Tobin, Amjad Alkodsi, Ikram Ullah, Gustav Stålhammar, Eva Karlsson, Thomas Hatschek, Johan Hartman, Sten Linnarsson, Jonas Bergh
BACKGROUND: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease...
February 12, 2018: BMC Cancer
F Runa, S Hamalian, K Meade, P Shisgal, P C Gray, J A Kelber
The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers...
December 2017: Current Molecular Biology Reports
Saskia Klutzny, Anna Anurin, Barbara Nicke, Joseph L Regan, Martin Lange, Luise Schulze, Karsten Parczyk, Patrick Steigemann
Cancer stem cells (CSCs) are involved in metastasis and resistance development, thus affecting anticancer therapy efficacy. The underlying pathways required for CSC maintenance and survival are not fully understood and only a limited number of treatment strategies to specifically target CSCs have been identified. To identify novel CSC targeting compounds, we here set-up an aldehyde dehydrogenase (ALDH)-based phenotypic screening system that allows for an automated and standardized identification of CSCs. By staining cancer cells for ALDH activity and applying high-content-based single-cell population analysis, the proportion of a potential CSC subpopulation with significantly higher ALDH activity (ALDHhigh) can be quantified in a heterogeneous cell population...
February 7, 2018: Cell Death & Disease
Simon R V Knott, Elvin Wagenblast, Showkhin Khan, Sun Y Kim, Mar Soto, Michel Wagner, Marc-Olivier Turgeon, Lisa Fish, Nicolas Erard, Annika L Gable, Ashley R Maceli, Steffen Dickopf, Evangelia K Papachristou, Clive S D'Santos, Lisa A Carey, John E Wilkinson, J Chuck Harrell, Charles M Perou, Hani Goodarzi, George Poulogiannis, Gregory J Hannon
Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse...
February 7, 2018: Nature
Tao Wan, Jing Shao, Bin Hu, Gang Liu, Peng Luo, Yanming Zhou
Background and objective: HSF1 is reported to be overexpressed in various solid tumors and play a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of HSF1 in patients with solid tumors. Methods: An extensive electronic search of three databases was performed for relevant articles. The pooled hazard ratios (HRs) or odds ratios with their corresponding 95% CI were calculated with a random-effects model. Heterogeneity and publication bias analyses were also conducted...
2018: OncoTargets and Therapy
Gábor Cserni, Ewa Chmielik, Bálint Cserni, Tibor Tot
This review describes the changes that have been implemented in the Tumor-Node-Metastasis (TNM)-based staging of breast cancers by the new, 8th editions of the relevant Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) publications. After giving a background for TNM being the common language of cancer staging and related activities like cancer treatment and registration, it summarizes not only the changes but reviews some highlights important for pathologists, and lists and comments on the differences between the publications and diagnostic practices based on them...
January 27, 2018: Virchows Archiv: An International Journal of Pathology
Ruikai Du, Bingjie Liu, Lei Zhou, Dong Wang, Xueyan He, Xiaojun Xu, Lixing Zhang, Chaoshi Niu, Suling Liu
Annexin A3 (ANXA3) is dysregulated and plays an important role in various cancers. However, the role of ANXA3 in breast cancer is still unclear. Here, we observed that the expression level of ANXA3 was significantly upregulated in breast cancer tissues. ANXA3 knockdown inhibited cell invasion but promoted cell proliferation in both in vitro and in vivo assays. Furthermore, we found that ANXA3 knockdown inhibited the NFκB pathway via upregulating IκBα, resulting in mesenchymal-epithelial transition (MET) and a heterogeneity change of breast cancer stem cells (BCSCs)...
January 26, 2018: Cell Death & Disease
Izabella Dolka, Michał Czopowicz, Anna Gruk-Jurka, Agata Wojtkowska, Rafał Sapierzyński, Piotr Jurka
Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson's grading system-established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material-to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson's grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson's grading system and cytological background details with metastases, and patients' survival...
2018: PloS One
Ying Wang, Shan Shao, Minna Luo, Shangke Huang, Lu Feng, Na Yuan, Fang Wu, Chengxue Dang, Xinhan Zhao
Breast cancer is a heterogeneous disease that can be classified into several molecular intrinsic subtypes according to hormone markers, including estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Breast cancer cases with different hormone status vary with respect to patient morbidity, metastasis organotropism and disease progression. It is well known that the most preferential relapse site of breast cancer is in the bone, but the metastatic incidence is markedly higher in hormone receptor-positive cancer compared with that in hormone receptor-negative cancers...
December 2017: Oncology Letters
Arja Ray, Rachel K Morford, Nima Ghaderi, David J Odde, Paolo P Provenzano
Carcinoma cells frequently expand and invade from a confined lesion, or multicellular clusters, into and through the stroma on the path to metastasis, often with an efficiency dictated by the architecture and composition of the microenvironment. Specifically, in desmoplastic carcinomas such as those of the breast, aligned collagen tracks provide contact guidance cues for directed cancer cell invasion. Yet, the evolving dynamics of this process of invasion remains poorly understood, in part due to difficulties in continuously capturing both spatial and temporal heterogeneity and progression to invasion in experimental systems...
January 17, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Song Shen, Yue Zhang, Kai-Ge Chen, Ying-Li Luo, Jun Wang
Accumulating evidence has confirmed that malignant tumors have a complex microenvironment, which consists of a heterogeneous collection of tumor cells and other cell subsets (including the full gamut of immune cells). Tumor-associated macrophages (TAMs), derived from circulating Ly6Chi monocytes, constitute the most substantial fraction of tumor-infiltrating immune cells in nearly all cancer types and contribute to tumor progression, vascularization, metastasis, immunosuppression and therapeutic resistance...
January 16, 2018: Molecular Pharmaceutics
Catharina Melzer, Juliane von der Ohe, Ralf Hass
BACKGROUND: Fusion of breast cancer cells with tumor-associated populations of the microenvironment including mesenchymal stroma/stem-like cells (MSC) represents a rare event in cell communication whereby the metastatic capacity of those hybrid cells remains unclear. METHODS: Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation between primary human MSC and human MDA-MB-231 breast cancer cells. Thus, lentiviral eGFP-labeled MSC and breast cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells after co-culture...
January 5, 2018: Cell Communication and Signaling: CCS
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