scholarly journals The Tumor Microenvironment as a Driving Force of Breast Cancer Stem Cell Plasticity

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3863
Author(s):  
Flavia Fico ◽  
Albert Santamaria-Martínez
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Selective Pressure ◽  
Transformed Cells ◽  
Intrinsic Properties ◽  
Cell Plasticity ◽  
Metastatic Colonization ◽  
Major Player ◽  
Cellular Hierarchy

Tumor progression involves the co-evolution of transformed cells and the milieu in which they live and expand. Breast cancer stem cells (BCSCs) are a specialized subset of cells that sustain tumor growth and drive metastatic colonization. However, the cellular hierarchy in breast tumors is rather plastic, and the capacity to transition from one cell state to another depends not only on the intrinsic properties of transformed cells, but also on the interplay with their niches. It has become evident that the tumor microenvironment (TME) is a major player in regulating the BCSC phenotype and metastasis. The complexity of the TME is reflected in its number of players and in the interactions that they establish with each other. Multiple types of immune cells, stromal cells, and the extracellular matrix (ECM) form an intricate communication network with cancer cells, exert a highly selective pressure on the tumor, and provide supportive niches for BCSC expansion. A better understanding of the mechanisms regulating these interactions is crucial to develop strategies aimed at interfering with key BCSC niche factors, which may help reducing tumor heterogeneity and impair metastasis.

scholarly journals Stromal cells in tumor microenvironment and breast cancer

2012 ◽  
Vol 32 (1-2) ◽  
pp. 303-315 ◽  
Author(s):  
Yan Mao ◽  
Evan T. Keller ◽  
David H. Garfield ◽  
Kunwei Shen ◽  
Jianhua Wang
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells

scholarly journals Research Progress on the Role of Regulatory T Cell in Tumor Microenvironment in the Treatment of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianyu Liu ◽  
Xueying Wang ◽  
Yuhan Deng ◽  
Xin Yu ◽  
Hongbin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Predictive Marker ◽  
Research Progress ◽  
Cancer Subtypes ◽  
Novel Treatments ◽  
Complex Ecosystem ◽  
The Impact

The tumor microenvironment (TME) is a complex ecosystem comprised of cancer cells, stromal cells, and immune cells. Analysis of the composition of TME is essential to assess the prognosis of patients with breast cancer (BC) and the efficacy of different regimes. Treg plays a crucial role in the microenvironment of breast cancer subtypes, and its function contributes to the development and progression of BC by suppressing anti-tumor immunity directly or indirectly through multiple mechanisms. In addition, conventional treatments, such as anthracycline-based neoadjuvant chemotherapy, and neo-therapies, such as immune-checkpoint blockades, have a significant impact on the absence of Tregs in BC TME, thus gaining additional anti-tumor effect to some extent. Strikingly, Treg in BC TME revealed the predicted efficacy of some therapeutic strategies. All these results suggest that we can manipulate the abundance of Treg to achieve the ultimate effect of both conventional and novel treatments. In this review, we discuss new insights into the characteristics of Treg in BC TME, the impact of different regiments on Treg, and the possibilities of Treg as a predictive marker of efficacy for certain treatments.

Abstract 1514: The Warburg effect in stromal cells drives breast cancer cell plasticity via interleukin 6

2012 ◽  
Author(s):  
Pasquale Sansone ◽  
Claudio Ceccarelli ◽  
Gianluca Storci ◽  
Marjan Berishaj ◽  
Monica Cricca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Stromal Cells ◽  
Interleukin 6 ◽  
Warburg Effect ◽  
Cell Plasticity ◽  
The Warburg Effect

scholarly journals Three-dimensional models of breast cancer–fibroblasts interactions

2020 ◽  
Vol 245 (10) ◽  
pp. 879-888
Author(s):  
Sunil Singh ◽  
Sydnie Tran ◽  
Justin Putman ◽  
Hossein Tavana
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Three Dimensional ◽  
Tumor Stroma ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Tumor Models ◽  
Primary Tumors

Tumor microenvironment is a complex niche consisting of cancer cells and stromal cells in a network of extracellular matrix proteins and various soluble factors. Dynamic interactions among cellular and non-cellular components of the tumor microenvironment regulate tumor initiation and progression. Fibroblasts are the most abundant stromal cell type and dynamically interact with cancer cells both in primary tumors and in metastases. Cancer cells activate resident fibroblasts to produce and secrete soluble signaling molecules that support proliferation, migration, matrix invasion, and drug resistance of cancer cell and tumor angiogenesis. In recent years, various forms of three-dimensional tumor models have been developed to study tumor–stromal interactions and to identify anti-cancer drugs that block these interactions. There is currently a technological gap in development of tumor models that are physiologically relevant, scalable, and allow convenient, on-demand addition of desired components of the tumor microenvironment. In this review, we discuss three studies from our group that focus on developing bioengineered models to study tumor-stromal signaling. We will present these studies chronologically and based on their increasing complexity. We will discuss the validation of the models using a CXCL12-CXCR4 chemokine-receptor signaling present among activated fibroblasts and breast cancer cells in solid tumors, highlight the advantages and shortcomings of the models, and conclude with our perspectives on their applications. Impact statement Tumor stroma plays an important role in progression of cancers to a fatal metastatic disease. Modern treatment strategies are considering targeting tumor stroma to improve outcomes for cancer patients. A current challenge to develop stroma-targeting therapeutics is the lack of preclinical physiologic tumor models. Animal models widely used in cancer research lack human stroma and are not amenable to screening of chemical compounds for cancer drug discovery. In this review, we outline in vitro three-dimensional tumor models that we have developed to study the interactions among cancer cells and stromal cells. We describe development of the tumor models in a modular fashion, from a spheroid model to a sophisticated organotypic model, and discuss the importance of using correct physiologic models to recapitulate tumor-stromal signaling. These biomimetic tumor models will facilitate understanding of tumor-stromal signaling biology and provide a scalable approach for testing and discovery of cancer drugs.

scholarly journals Breast Cancer Drug Resistance: Overcoming the Challenge by Capitalizing on MicroRNA and Tumor Microenvironment Interplay

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3691
Author(s):  
Giulia Cosentino ◽  
Ilaria Plantamura ◽  
Elda Tagliabue ◽  
Marilena V. Iorio ◽  
Alessandra Cataldo
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Triple Negative ◽  
Response To Therapy ◽  
Cancer Drug ◽  
Tumor Aggressiveness ◽  
Her2 Positive ◽  
Cancer Drug Resistance ◽  
Positive Breast Cancer

The clinical management of breast cancer reaches new frontiers every day. However, the number of drug resistant cases is still high, and, currently, this constitutes one of the major challenges that cancer research has to face. For instance, 50% of women affected with HER2 positive breast cancer presents or acquires resistance to trastuzumab. Moreover, for patients affected with triple negative breast cancer, standard chemotherapy is still the fist-line therapy, and often patients become resistant to treatments. Tumor microenvironment plays a crucial role in this context. Indeed, cancer-associated stromal cells deliver oncogenic cues to the tumor and vice versa to escape exogenous insults. It is well known that microRNAs are among the molecules exploited in this aberrant crosstalk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we summarize the most recent literature regarding the involvement of miRNAs in the crosstalk between tumor and stromal cells and their capability to modulate tumor microenvironment characteristics. All up-to-date findings suggest that microRNAs in the TME could serve both to reverse malignant phenotype of stromal cells, modulating response to therapy, and as predictive/prognostic biomarkers.

scholarly journals The Breast Tumor Microenvironment: A Key Player in Metastatic Spread

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4798
Author(s):  
Lucas E. L. Terceiro ◽  
Chidalu A. Edechi ◽  
Nnamdi M. Ikeogu ◽  
Barbara E. Nickel ◽  
Sabine Hombach-Klonisch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Spread ◽  
Paracrine Factors ◽  
Primary Tumor Site

The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.

scholarly journals Exploration of Tumor Microenvironment-Related Biomarkers for the Prognosis of Triple Negative Breast Cancer

2021 ◽  
Author(s):  
Xiaorui Han ◽  
Zaiyi Liu ◽  
Changhong Liang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Stromal Cells ◽  
Prognostic Model ◽  
Triple Negative ◽  
High Efficiency ◽  
Functional Enrichment

Abstract Background: Triple negative breast cancer (TNBC) is one of the most disastrous breast cancer subtypes world widely. The tumor microenvironment (TME), especially the infiltration of immune and stromal cells, are highly related to the occurrence, development and prognosis of breast cancer. Therefore, exploration of TME-related biomarkers is greatly important for improving overall survival rate of TNBC patients. Methods: The open-assess Cancer Genome Atlas (TCGA) database provides gene expression profile for a variety of malignant tumors allowing researchers to explore genes demonstrating TME in the prognosis prediction of TNBC. In our present study, ESTIMATE algorithm was used to calculate the immune and stromal scores in accordance with the characteristics of specific genes in immune and stromal cells, and divide them into high and low-score groups. Limma R package was then utilized to screen differentially expressed genes (DEGs). After that, functional enrichment analysis and protein-protein interaction (PPI) network were performed to explore the bio-information of the DEGs and their encoded proteins. Subsequently, the identified these genes were further verified in the Gene Expression Omnibus (GEO) datasets. Results: Eight genes, including ACAP1, DUSP1, LYZGZMA, SASH3, CCL5, CD74, and DPT, were explored to closely related to the TME of TNBC. A prognostic model containing these selected genes was established with a high efficiency in the prediction of the poor prognosis of TNBC patients.Conclusion: An eight-gene prognostic model was a considerably reliable approach for predicting the overall survival of TNBC patients, and could help clinicians selecting personalized treatments for their TNBC patients.

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