scholarly journals Tumor Microenvironment

Medicina ◽  
2019 ◽  
Vol 56 (1) ◽  
pp. 15 ◽  
Author(s):  
Borros Arneth
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Development ◽  
Tumor Vasculature ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
Positive Health ◽  
Positive Health Outcomes ◽  
Uncontrolled Cell Proliferation ◽  
Significant Attention ◽  
Malignant Behavior

Background and Objectives: The tumor microenvironment has been widely implicated in tumorigenesis because it harbors tumor cells that interact with surrounding cells through the circulatory and lymphatic systems to influence the development and progression of cancer. In addition, nonmalignant cells in the tumor microenvironment play critical roles in all the stages of carcinogenesis by stimulating and facilitating uncontrolled cell proliferation. Aim: This study aims to explore the concept of the tumor microenvironment by conducting a critical review of previous studies on the topic. Materials and Methods: This review relies on evidence presented in previous studies related to the topic. The articles included in this review were obtained from different medical and health databases. Results and Discussion: The tumor microenvironment has received significant attention in the cancer literature, with a particular focus on its role in tumor development and progression. Previous studies have identified various components of the tumor microenvironment that influence malignant behavior and progression. In addition to malignant cells, adipocytes, fibroblasts, tumor vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts are present in the tumor microenvironment. Each of these cell types has unique immunological capabilities that determine whether the tumor will survive and affect neighboring cells. Conclusion: The tumor microenvironment harbors cancer stem cells and other molecules that contribute to tumor development and progression. Consequently, targeting and manipulating the cells and factors in the tumor microenvironment during cancer treatment can help control malignancies and achieve positive health outcomes.

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 Matrix Remodeling and Hyaluronan Production by Myofibroblasts and Cancer-Associated Fibroblasts in 3D Collagen Matrices

Gels ◽  
2020 ◽  
Vol 6 (4) ◽  
pp. 33
Author(s):  
Jiranuwat Sapudom ◽  
Claudia Damaris Müller ◽  
Khiet-Tam Nguyen ◽  
Steve Martin ◽  
Ulf Anderegg ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Average Molecular Weight ◽  
Cell Types ◽  
Dermal Fibroblasts ◽  
Matrix Remodeling ◽  
Cancer Associated Fibroblasts ◽  
Collagen Matrices ◽  
3D Collagen ◽  
Tgf Β1

The tumor microenvironment is a key modulator in cancer progression and has become a novel target in cancer therapy. An increase in hyaluronan (HA) accumulation and metabolism can be found in advancing tumor progression and are often associated with aggressive malignancy, drug resistance and poor prognosis. Wound-healing related myofibroblasts or activated cancer-associated fibroblasts (CAF) are assumed to be the major sources of HA. Both cell types are capable to synthesize new matrix components as well as reorganize the extracellular matrix. However, to which extent myofibroblasts and CAF perform these actions are still unclear. In this work, we investigated the matrix remodeling and HA production potential in normal human dermal fibroblasts (NHFB) and CAF in the absence and presence of transforming growth factor beta -1 (TGF-β1), with TGF-β1 being a major factor of regulating fibroblast differentiation. Three-dimensional (3D) collagen matrix was utilized to mimic the extracellular matrix of the tumor microenvironment. We found that CAF appeared to response insensitively towards TGF-β1 in terms of cell proliferation and matrix remodeling when compared to NHFB. In regards of HA production, we found that both cell types were capable to produce matrix bound HA, rather than a soluble counterpart, in response to TGF-β1. However, activated CAF demonstrated higher HA production when compared to myofibroblasts. The average molecular weight of produced HA was found in the range of 480 kDa for both cells. By analyzing gene expression of HA metabolizing enzymes, namely hyaluronan synthase (HAS1-3) and hyaluronidase (HYAL1-3) isoforms, we found expression of specific isoforms in dependence of TGF-β1 present in both cells. In addition, HAS2 and HYAL1 are highly expressed in CAF, which might contribute to a higher production and degradation of HA in CAF matrix. Overall, our results suggested a distinct behavior of NHFB and CAF in 3D collagen matrices in the presence of TGF-β1 in terms of matrix remodeling and HA production pointing to a specific impact on tumor modulation.

scholarly journals Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression

2019 ◽  
Vol 20 (19) ◽  
pp. 4719 ◽  
Author(s):  
Chloé Laplagne ◽  
Marcin Domagala ◽  
Augustin Le Naour ◽  
Christophe Quemerais ◽  
Dimitri Hamel ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Small Molecules ◽  
Tumor Development ◽  
Cell Types ◽  
Host Cells ◽  
Matrix Proteins ◽  
Cancer Cell Survival ◽  
Cancer Setting ◽  
Interfering Rna ◽  
Stromal Stem Cells

The tumor bulk is composed of a highly heterogeneous population of cancer cells, as well as a large variety of resident and infiltrating host cells, extracellular matrix proteins, and secreted proteins, collectively known as the tumor microenvironment (TME). The TME is essential for driving tumor development by promoting cancer cell survival, migration, metastasis, chemoresistance, and the ability to evade the immune system responses. Therapeutically targeting tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), regulatory T-cells (T-regs), and mesenchymal stromal/stem cells (MSCs) is likely to have an impact in cancer treatment. In this review, we focus on describing the normal physiological functions of each of these cell types and their behavior in the cancer setting. Relying on the specific surface markers and secreted molecules in this context, we review the potential targeting of these cells inducing their depletion, reprogramming, or differentiation, or inhibiting their pro-tumor functions or recruitment. Different approaches were developed for this targeting, namely, immunotherapies, vaccines, small interfering RNA, or small molecules.

scholarly journals Role of Regular Physical Exercise in Tumor Vasculature: Favorable Modulator of Tumor Milieu

2020 ◽  
Author(s):  
Mário Esteves ◽  
Mariana P. Monteiro ◽  
Jose Alberto Duarte
Keyword(s):  
Tumor Microenvironment ◽  
Physical Exercise ◽  
Immune Cells ◽  
Fluid Pressure ◽  
Tumor Development ◽  
Tumor Vasculature ◽  
Vascular Conductance ◽  
Transient Nature ◽  
Underlying Mechanisms ◽  
Regular Physical Exercise

AbstractThe tumor vessel network has been investigated as a precursor of an inhospitable tumor microenvironment, including its repercussions in tumor perfusion, oxygenation, interstitial fluid pressure, pH, and immune response. Dysfunctional tumor vasculature leads to the extravasation of blood to the interstitial space, hindering proper perfusion and causing interstitial hypertension. Consequently, the inadequate delivery of oxygen and clearance of by-products of metabolism promote the development of intratumoral hypoxia and acidification, hampering the action of immune cells and resulting in more aggressive tumors. Thus, pharmacological strategies targeting tumor vasculature were developed, but the overall outcome was not satisfactory due to its transient nature and the higher risk of hypoxia and metastasis. Therefore, physical exercise emerged as a potential favorable modulator of tumor vasculature, improving intratumoral vascularization and perfusion. Indeed, it seems that regular exercise practice is associated with lasting tumor vascular maturity, reduced vascular resistance, and increased vascular conductance. Higher vascular conductance reduces intratumoral hypoxia and increases the accessibility of circulating immune cells to the tumor milieu, inhibiting tumor development and improving cancer treatment. The present paper describes the implications of abnormal vasculature on the tumor microenvironment and the underlying mechanisms promoted by regular physical exercise for the re-establishment of more physiological tumor vasculature.

scholarly journals Obesity-Related Fatty Acid and Cholesterol Metabolism in Cancer-Associated Host Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Ying Ye ◽  
Xiaoting Sun ◽  
Yongtian Lu
Keyword(s):  
Endothelial Cells ◽  
Fatty Acid ◽  
Tumor Microenvironment ◽  
Metabolic Regulation ◽  
Cholesterol Metabolism ◽  
Tumor Development ◽  
Host Cells ◽  
Acid Oxidation ◽  
Cancer Associated Fibroblasts ◽  
Future Perspectives

Obesity-derived disturbances in fatty acid and cholesterol metabolism are linked to numerous diseases, including various types of malignancy. In tumor cells, metabolic alterations have been long recognized and intensively studied. However, metabolic changes in host cells in the tumor microenvironment and their contribution to tumor development have been largely overlooked. During the last decade, research advances show that fatty acid oxidation, cholesterol metabolism, and lipid accumulation play critical roles in cancer-associated host cells such as endothelial cells, lymph endothelial cells, cancer-associated fibroblasts, tumor-associated myeloid cells, and tumor-associated lymphocytes. In addition to anti-angiogenic therapies and immunotherapy that have been practiced in the clinic, metabolic regulation is considered another promising cancer therapy targeting non-tumor host cells. Understanding the obesity-associated metabolism changes in cancer-associated host cells may ultimately be translated into therapeutic options that benefit cancer patients. In this mini-review, we briefly summarize the lipid metabolism associated with obesity and its role in host cells in the tumor microenvironment. We also discuss the current understanding of the molecular pathways involved and future perspectives to benefit from this metabolic complexity.

scholarly journals MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5604
Author(s):  
Shine-Gwo Shiah ◽  
Sung-Tau Chou ◽  
Jang-Yang Chang
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Cell Communication ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Therapeutic Implications ◽  
Rna Molecules ◽  
Non Coding Rna

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.

scholarly journals The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenqi Ti ◽  
Jianbo Wang ◽  
Yufeng Cheng
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblasts ◽  
Protein Coding ◽  
Sequencing Technologies ◽  
Integral Role ◽  
Tumor Growth And Metastasis

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.

scholarly journals Cancer: a mirrored room between tumor bulk and tumor microenvironment

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Pablo Hernández-Camarero ◽  
Elena López-Ruiz ◽  
Juan Antonio Marchal ◽  
Macarena Perán
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Development ◽  
Cell Types ◽  
Molecular Signature ◽  
Therapeutic Approaches ◽  
Metastatic Niche ◽  
Systematic Analysis ◽  
Tumor Mass ◽  
Functional Transformations

AbstractIt has been well documented that the tumor microenvironment (TME) plays a key role in the promotion of drug resistance, the support of tumor progression, invasiveness, metastasis, and even the maintenance of a cancer stem-like phenotype. Here, we reviewed TME formation presenting it as a reflection of a tumor’s own organization during the different stages of tumor development. Interestingly, functionally different groups of stromal cells seem to have specific spatial distributions within the TME that change as the tumor evolves into advanced stage progression which correlates with the fact that cancer stem-like cells (CSCs) are located in the edges of solid tumor masses in advanced tumors.We also focus on the continuos feedback that is established between a tumor and its surroundings. The “talk” between tumor mass cells and TME stromal cells, marks the evolution of both interlocuting cell types. For instance, the metabolic and functional transformations that stromal cells undergo due to tumor corrupting activity.Moreover, the molecular basis of metastatic spread is also approached, making special emphasis on the site-specific pre-metastatic niche formation as another reflection of the primary tumor molecular signature.Finally, several therapeutic approaches targeting primary TME and pre-metastatic niche are suggested. For instance, a systematic analysis of the TME just adjacent to the tumor mass to establish the proportion of myofibroblasts-like cancer-associated fibroblasts (CAFs) which may in turn correspond to stemness and metastases-promotion. Or the implementation of “re-education” therapies consisting of switching tumor-supportive stromal cells into tumor-suppressive ones. In summary, to improve our clinical management of cancer, it is crucial to understand and learn how to manage the close interaction between TME and metastasis.

Normalization of tumor microvasculature basing on targeting and modulation of tumor microenvironment

Nanoscale ◽  
2021 ◽  
Author(s):  
Zhipeng Li ◽  
Fang Ning ◽  
Changduo Wang ◽  
Hongli Yu ◽  
Qingming Ma ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Development ◽  
Compressive Force ◽  
Tumor Vasculature ◽  
Angiogenic Factors ◽  
Tumor Microvasculature

Angiogenesis is an essential process for tumor development. Owing to imbalance of pro- and anti-angiogenic factors, the tumor vasculature possesses the characteristics of tortuous, hyperpermeable vessels and compressive force, resulting...

scholarly journals miRNAs derived from cancer-associated fibroblasts in colorectal cancer

Epigenomics ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 1627-1645 ◽  
Author(s):  
Amir Savardashtaki ◽  
Zahra Shabaninejad ◽  
Ahmad Movahedpour ◽  
Roxana Sahebnasagh ◽  
Hamed Mirzaei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Development ◽  
Complex Interaction ◽  
Cancer Associated Fibroblasts ◽  
Paracrine Signaling ◽  
Cancer Stroma ◽  
The World ◽  
First Time

Currently, the incidence of colorectal cancer (CRC) is increasing across the world. The cancer stroma exerts an impact on the spread, invasion and chemoresistance of CRC. The tumor microenvironment involves a complex interaction between cancer cells and stromal cells, for example, cancer-associated fibroblasts (CAFs). CAFs can promote neoplastic angiogenesis and tumor development in CRC. Mounting evidence suggests that many miRNAs are overexpressed (miR-21, miR-329, miR-181a, miR-199a, miR-382 and miR-215) in CRC CAFs, and these miRNAs can influence the spread, invasiveness and chemoresistance in neighboring tumor cells via paracrine signaling. Herein, we summarize the pathogenic roles of miRNAs and CAFs in CRC. Moreover, for first time, we highlight the miRNAs derived from CRC-associated CAFs and their roles in CRC pathogenesis.

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