scholarly journals A Role for Adipocytes and Adipose Stem Cells in the Breast Tumor Microenvironment and Regenerative Medicine

2021 ◽  
Vol 12 ◽  
Author(s):  
Courtney K. Brock ◽  
Katherine L. Hebert ◽  
Maria Artiles ◽  
Maryl K. Wright ◽  
Thomas Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Regenerative Medicine ◽  
Cancer Progression ◽  
Cell Types ◽  
Adipose Stem Cells ◽  
Physiological Level ◽  
Physical Support ◽  
Poor Outcomes

Obesity rates are climbing, representing a confounding and contributing factor to many disease states, including cancer. With respect to breast cancer, obesity plays a prominent role in the etiology of this disease, with certain subtypes such as triple-negative breast cancer having a strong correlation between obesity and poor outcomes. Therefore, it is critical to examine the obesity-related alterations to the normal stroma and the tumor microenvironment (TME). Adipocytes and adipose stem cells (ASCs) are major components of breast tissue stroma that have essential functions in both physiological and pathological states, including energy storage and metabolic homeostasis, physical support of breast epithelial cells, and directing inflammatory and wound healing responses through secreted factors. However, these processes can become dysregulated in both metabolic disorders, such as obesity and also in the context of breast cancer. Given the well-established obesity-neoplasia axis, it is critical to understand how interactions between different cell types in the tumor microenvironment, including adipocytes and ASCs, govern carcinogenesis, tumorigenesis, and ultimately metastasis. ASCs and adipocytes have multifactorial roles in cancer progression; however, due to the plastic nature of these cells, they also have a role in regenerative medicine, making them promising tools for tissue engineering. At the physiological level, the interactions between obesity and breast cancer have been examined; here, we will delineate the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment. We will define the current state of understanding of how adipocytes and ASCs contribute to tumor progression through their role in the tumor microenvironment and how this is altered in the context of obesity. We will also introduce recent developments in utilizing adipocytes and ASCs in novel approaches to breast reconstruction and regenerative medicine.

scholarly journals miR-216a Acts as a Negative Regulator of Breast Cancer by Modulating Stemness Properties and Tumor Microenvironment

2020 ◽  
Vol 21 (7) ◽  
pp. 2313 ◽  
Author(s):  
Giuseppina Roscigno ◽  
Assunta Cirella ◽  
Alessandra Affinito ◽  
Cristina Quintavalle ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Negative Regulator ◽  
Mammosphere Formation ◽  
Incidence And Mortality ◽  
Cells Of The Microenvironment

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.

scholarly journals IMPORTANCIA DEL MICROAMBIENTE TUMORAL EN LA PROGRESIÓN DEL CÁNCER DE MAMA

2019 ◽  
pp. 1-7
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Breast Cancer Progression ◽  
Cáncer De Mama ◽  
Cytokine Network

IMPORTANCIA DEL MICROAMBIENTE TUMORAL EN LA PROGRESIÓN DEL CÁNCER DE MAMA IMPORTANCE OF TUMOR MICROENVIRONMENT IN BREAST CANCER PROGRESSION Julio E. Valdivia-Silvaa, Eduardo García-Zepedab DOI: https://doi.org/10.33017/RevECIPeru2008.0005/ RESUMEN El microambiente tumoral, en el cáncer de mama y otros de estirpe epitelial, es un tejido complejo que comprende diferentes tipos celulares que incluyen las células tumorales, fibroblastos, células endoteliales, y leucocitos infiltrantes. Citocinas, quimiocinas, factores de crecimiento y proteasas son moléculas claves que controlan la comunicación autocrina y paracrina entre estas células individuales. Bajo algunas circunstancias, dichas moléculas pueden orquestar respuestas del hospedero contra el tumor, pero contradictoriamente existe evidencia que demuestra un rol paradójico que contribuye al crecimiento y progresión de la neoplasia además de inmunosupresión local. Adicionalmente, la progresión del cáncer de mama está asociada con una robusta neovascularización. Es claro que las células “normales” asociadas al tumor, como las inmunes, endoteliales y del estroma, conspiran con las cancerosas en promover este proceso. En ésta revisión enfocamos algunas de las acciones de citocinas inflamatorias y otras moléculas del microambiente tumoral sobre el comportamiento invasivo y metastásico del carcinoma mamario. Una mayor comprensión de estos tipos celulares y constituyentes moleculares del microambiente pueden ser usados en el diseño de terapias más efectivas contra el cáncer. Palabras clave: cáncer de mama, microambiente tumoral, metástasis, inflamación. ABSTRACT The epithelial tumour microenvironment is a complex tissue comprising variable numbers of tumour cells, fibroblasts, endothelial cells and infiltrating leucocytes. Cytokines, chemokines, growth factors, and proteases are key molecules controlling autocrine or paracrine communications within and between these individual cell types. Under some circumstances, endogenous cytokines may orchestrate host responses against the tumour, but there is increasing evidence that the cytokine network contributes to tumour growth, progression and host immuno-suppression. In addition, breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated „normal‟ cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In this review we outline some of the actions of endogenous inflammatory cytokines and other molecules in tumor microenvironment over metastatic and invasive behavior of the breast carcinoma. A better understanding of these various cellular and molecular constituents of breast cancer microenvironment may be useful in designing more effective therapies. Keywords: breast cancer, tumour microenvironment, metastasis, inflammation.

scholarly journals CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression

2019 ◽  
Vol 143 (3) ◽  
pp. 747-756 ◽  
Author(s):  
Ruya Zhao ◽  
Rayan Kaakati ◽  
Xinjian Liu ◽  
Lingfan Xu ◽  
Andrew K. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Adipose Stem Cells ◽  
Promote Breast Cancer

scholarly journals Cancer-associated adipocytes: key players in breast cancer progression

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Qi Wu ◽  
Bei Li ◽  
Zhiyu Li ◽  
Juanjuan Li ◽  
Si Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tumor Biology ◽  
Active Role ◽  
Cell Types ◽  
Functional Changes ◽  
Cell Crosstalk

Abstract Adipocytes are one of the primary stromal cells in many tissues, and they are considered to play an active role in the tumor microenvironment. Cancer-associated adipocytes (CAAs) are not only found adjacent to cancer cells, but also communicate with cancer cells through releasing various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Indeed, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, is becoming pandemic in some countries and it is now considered to be an independent risk factor for cancer progression. In this review, we focus on the potential mechanisms involved with special attention to the adipocyte-cancer cell circle in breast cancer. We envisage that besides having a direct impact on tumor cells, CAAs systemically preconditions the tumor microenvironment by favoring anti-tumor immunity. A better understanding of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and permit the optimization of therapeutic strategies.

Obesity-altered adipose stem cells promote breast cancer progression and metastasis

Cytotherapy ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. S30
Author(s):  
B.A. Bunnell ◽  
R. Sabol ◽  
A.L. Strong ◽  
M.E. Burow
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Adipose Stem Cells ◽  
Promote Breast Cancer

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

2021 ◽  
Vol 22 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Ezzatollah Fathi ◽  
Ayoub Mamandi ◽  
Raheleh Farahzadi ◽  
Hamid Reza Heidari
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Therapeutic Interventions ◽  
Tumorigenic Potential ◽  
Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 29 ◽  
Author(s):  
Jyun-Yuan Huang ◽  
Yen-Yun Wang ◽  
Steven Lo ◽  
Ling-Ming Tseng ◽  
Dar-Ren Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Progression ◽  
Human Breast Cancer ◽  
Breast Cancer Progression ◽  
Akt Pathway ◽  
Adipose Derived Stem Cells ◽  
Human Breast ◽  
Akt Inhibitor ◽  
Promoting Effect

Adipose-derived stem cells (ADSCs) have been implicated in tumor growth and metastasis in breast cancer. ADSCs exhibit tumor tropism, and are of increasing clinical relevance due to the autologous fat grafting for breast reconstruction. Although we have previously shown that a high level of the adipocytokine visfatin in human breast cancer tissues correlated with tumor progression mediated by cAbl and STAT3, the effects of visfatin in the tumor microenvironment are unclear. To understand how visfatin modulates breast cancer within the tumor-stromal environment, we examined determinants of breast cancer progression using a visfatin-primed ADSCs-tumor co-culture model. ADSCs were isolated from tumor-free adipose tissue adjacent to breast tumors. ADSCs were treated with or without visfatin for 48 h and then collected for co-culture with breast cancer cell line MDA-MB-231 for 72 h in a transwell system. We found that the MDA-MB-231 cells co-cultured with visfatin-treated ADSCs (vADSCs) had higher levels of cell viability, anchorage independent growth, migration, invasion, and tumorsphere formation than that co-cultured with untreated ADSCs (uADSCs). Growth differentiation factor 15 (GDF15) upregulation was found in the co-culture conditioned medium, with GDF15 neutralizing antibody blocking the promoting effect on MDA-MB-231 in co-culture. In addition, a GDF15-induced AKT pathway was found in MDA-MB-231 and treatment with PI3K/AKT inhibitor also reversed the promoting effect. In an orthotopic xenograft mouse model, MDA-MB-231 co-injected with vADSCs formed a larger tumor mass than with uADSCs. Positive correlations were noted between visfatin, GDF15, and phosphor-AKT expressions in human breast cancer specimens. In conclusion, visfatin activated GDF15-AKT pathway mediated via ADSCs to facilitate breast cancer progression.

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