Tumor microenvironment: The role of the tumor stroma in cancer

2007 ◽  
Vol 101 (4) ◽  
pp. 805-815 ◽  
Author(s):  
Hanchen Li ◽  
Xueli Fan ◽  
JeanMarie Houghton
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Stroma

scholarly journals Role of MSC in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2107 ◽  
Author(s):  
Ralf Hass
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Cell Types ◽  
Cellular Interactions ◽  
Cell Functions ◽  
Metastatic Behavior ◽  
Stem Cell Niches

The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor’s metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma.

scholarly journals The Role of Extracellular Vesicles in Cancer: Cargo, Function, and Therapeutic Implications

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 93 ◽  
Author(s):  
James Jabalee ◽  
Rebecca Towle ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Tumor Stroma ◽  
Therapeutic Implications ◽  
Membrane Bound ◽  
Immune Destruction ◽  
And Function ◽  
Cargo Molecule

Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound structures that play key roles in intercellular communication. EVs are potent regulators of tumorigenesis and function largely via the shuttling of cargo molecules (RNA, DNA, protein, etc.) among cancer cells and the cells of the tumor stroma. EV-based crosstalk can promote proliferation, shape the tumor microenvironment, enhance metastasis, and allow tumor cells to evade immune destruction. In many cases these functions have been linked to the presence of specific cargo molecules. Herein we will review various types of EV cargo molecule and their functional impacts in the context of oncology.

scholarly journals Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2057 ◽  
Author(s):  
Shweta Joshi
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Genetic Alterations ◽  
Future Directions ◽  
Pediatric Tumor ◽  
Normal Tissues ◽  
Recent Advances ◽  
Future Potential

Neuroblastoma (NB) is the most common pediatric tumor malignancy that originates from the neural crest and accounts for more than 15% of all the childhood deaths from cancer. The neuroblastoma cancer research has long been focused on the role of MYCN oncogene amplification and the contribution of other genetic alterations in the progression of this malignancy. However, it is now widely accepted that, not only tumor cells, but the components of tumor microenvironment (TME), including extracellular matrix, stromal cells and immune cells, also contribute to tumor progression in neuroblastoma. The complexity of different components of tumor stroma and their resemblance with surrounding normal tissues pose huge challenges for therapies targeting tumor microenvironment in NB. Hence, the detailed understanding of the composition of the TME of NB is crucial to improve existing and future potential immunotherapeutic approaches against this childhood cancer. In this review article, I will discuss different components of the TME of NB and the recent advances in the strategies, which are used to target the tumor microenvironment in neuroblastoma.

scholarly journals Chemotherapy resistance and stromal targets in breast cancer treatment: a review

2020 ◽  
Vol 47 (10) ◽  
pp. 8169-8177
Author(s):  
Y. M. van der Spek ◽  
J. R. Kroep ◽  
R. A. E. M. Tollenaar ◽  
Wilma E. Mesker
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Chemotherapy Resistance ◽  
Tumor Stroma ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Specific Therapy ◽  
Primary Tumors ◽  
Cytokines And Chemokines

Abstract Therapy resistance is a known problem in breast cancer and is associated with a variety of mechanisms. The role of the tumor microenvironment in cancer development and resistance mechanisms is becoming increasingly understood. Tumor–stroma is the main component of the tumor microenvironment. Stromal cells like cancer-associated fibroblasts (CAFs) are believed to contribute to chemotherapy resistance via the production of several secreted factors like cytokines and chemokines. CAFs are found to influence disease progression; patients with primary tumors with a high amount of tumor–stroma have a significantly worse outcome. Therefore the role of CAFs resistance mechanisms makes them a promising target in anti-cancer therapy. An overview of recent advances in strategies to target breast cancer stroma is given and the current literature regarding these stromal targets is discussed. CAF-specific proteins as well as secreted molecules involved in tumor–stroma interactions provide possibilities for stroma-specific therapy. The development of stroma-specific therapy is still in its infancy and the available literature is limited. Within the scope of personalized treatment, biomarkers based on the tumor–stroma have future potential for the improvement of treatment via image-guided surgery (IGS) and PET scanning.

scholarly journals The Interplay of Autophagy and Tumor Microenvironment in Colorectal Cancer—Ways of Enhancing Immunotherapy Action

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 533 ◽  
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Georgia Kyriakopoulou ◽  
Athanasios G. Papavassiliou ◽  
Michalis V. Karamouzis
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Stroma ◽  
Cellular Functions ◽  
Different Types ◽  
Cellular Immune ◽  
Cellular Components ◽  
Catabolic Process

Autophagy as a primary homeostatic and catabolic process is responsible for the degradation and recycling of proteins and cellular components. The mechanism of autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions, and resistance to cancer therapy. A growing body of evidence suggests that autophagy is also a key regulator of the tumor microenvironment and cellular immune response in different types of cancer, including colorectal cancer (CRC). Furthermore, autophagy is responsible for initiating the immune response especially when it precedes cell death. However, the role of autophagy in CRC and the tumor microenvironment remains controversial. In this review, we identify the role of autophagy in tumor microenvironment regulation and the specific mechanism by which autophagy is implicated in immune responses during CRC tumorigenesis and the context of anticancer therapy.

scholarly journals Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 750 ◽  
Author(s):  
Deepshikha Mishra ◽  
Debabrata Banerjee
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Drug Targets ◽  
Cancer Metabolism ◽  
Tumor Stroma ◽  
Metabolic Enzyme ◽  
Ldh Activity ◽  
Lactate Dehydrogenases

Cancer is a metabolic disease in which abnormally proliferating cancer cells rewire metabolic pathways in the tumor microenvironment (TME). Molecular reprogramming in the TME helps cancer cells to fulfill elevated metabolic demands for bioenergetics and cellular biosynthesis. One of the ways through which cancer cell achieve this is by regulating the expression of metabolic enzymes. Lactate dehydrogenase (LDH) is the primary metabolic enzyme that converts pyruvate to lactate and vice versa. LDH also plays a significant role in regulating nutrient exchange between tumor and stroma. Thus, targeting human lactate dehydrogenase for treating advanced carcinomas may be of benefit. LDHA and LDHB, two isoenzymes of LDH, participate in tumor stroma metabolic interaction and exchange of metabolic fuel and thus could serve as potential anticancer drug targets. This article reviews recent research discussing the roles of lactate dehydrogenase in cancer metabolism. As molecular regulation of LDHA and LDHB in different cancer remains obscure, we also review signaling pathways regulating LDHA and LDHB expression. We highlight on the role of small molecule inhibitors in targeting LDH activity and we emphasize the development of safer and more effective LDH inhibitors. We trust that this review will also generate interest in designing combination therapies based on LDH inhibition, with LDHA being targeted in tumors and LDHB in stromal cells for better treatment outcome.

scholarly journals Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao Li ◽  
Hongming Zhu ◽  
Weixuan Sun ◽  
Xingru Yang ◽  
Qing Nie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Stroma ◽  
Cancer Associated Fibroblasts ◽  
Tumor Treatment ◽  
Nucleotide Synthesis ◽  
Nitrogenous Compounds ◽  
Therapeutic Implications ◽  
Cancer Initiation

AbstractCancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a “nitrogen reservoir” for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism.

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.

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