scholarly journals Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shangli Zhu ◽  
Ming Yi ◽  
Yuze Wu ◽  
Bing Dong ◽  
Kongming Wu
Keyword(s):  
Tumor Progression ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Promising Target ◽  
Multiple Processes ◽  
Enhance Tumor Cell ◽  
Patient Prognosis ◽  
Anti Tumor Activity

AbstractMacrophages are heterogeneous cells that present as different functional phenotypes due to their plasticity. They can be classified into two categories, namely M1- and M2-like macrophages, which are involved in processes as diverse as anti-tumor activity and immunosuppressive tumor promotion. Tumor-associated macrophages (TAMs) are defined as being of an M2-type and are considered as the active component in tumor microenvironment. TAMs are involved in multiple processes of tumor progression through the expression of cytokines, chemokines, growth factors, protein hydrolases and more, which lead to enhance tumor cell proliferation, angiogenesis, and immunosuppression, which in turn supports invasion and metastasis. It is assumed that the abundance of TAMs in major solid tumors is correlated to a negative patient prognosis. Because of the currently available data of the TAMs’ role in tumor development, these cells have emerged as a promising target for novel cancer treatment strategies. In this paper, we will briefly describe the origins and types of TAMs and will try to comprehensively show how TAMs contribute to tumorigenesis and disease progression. Finally, we will present the main TAM-based therapeutic strategies currently available.

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

scholarly journals CD147 Is a Promising Target of Tumor Progression and a Prognostic Biomarker

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1803 ◽  
Author(s):  
Alexandra Landras ◽  
Coralie Reger de Moura ◽  
Fanelie Jouenne ◽  
Celeste Lebbe ◽  
Suzanne Menashi ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Cancer Diagnosis ◽  
Tumor Development ◽  
Strategy Development ◽  
Tumor Biomarker ◽  
Diagnosis And Prognosis ◽  
Promising Target ◽  
Cd147 Expression

Microenvironment plays a crucial role in tumor development and progression. Cancer cells modulate the tumor microenvironment, which also contribute to resistance to therapy. Identifying biomarkers involved in tumorigenesis and cancer progression represents a great challenge for cancer diagnosis and therapeutic strategy development. CD147 is a glycoprotein involved in the regulation of the tumor microenvironment and cancer progression by several mechanisms—in particular, by the control of glycolysis and also by its well-known ability to induce proteinases leading to matrix degradation, tumor cell invasion, metastasis and angiogenesis. Accumulating evidence has demonstrated the role of CD147 expression in tumor progression and prognosis, suggesting it as a relevant tumor biomarker for cancer diagnosis and prognosis, as well as validating its potential as a promising therapeutic target in cancers.

scholarly journals Race as a Contributor to Stromal Modulation of Tumor Progression

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2656
Author(s):  
Mamatha Kakarla ◽  
Sathyavathi ChallaSivaKanaka ◽  
Simon W. Hayward ◽  
Omar E. Franco
Keyword(s):  
Tumor Progression ◽  
Racial Disparities ◽  
Tumor Biology ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Response To Treatment ◽  
Promising Area ◽  
Aggressive Tumor ◽  
Immunosuppressive Microenvironment ◽  
Personalized Cancer

Stromal cells play crucial roles in tumor development and are increasingly attractive targets for therapy. There are considerable racial disparities in the incidence and progression of many tumors, reflecting both environmental exposure and genetic differences existing between races. Tumorigenesis and tumor progression are linked to both the propensity to suffer an initiating event and the host response to such an event once it occurs, contributing to incidence and outcomes. In this review, we focused on racial disparities in the tumor microenvironment (TME) of different cancers as potential modulators of growth, metastasis, and response to treatment. Several studies suggest that the TME in AA has a distinct tumor biology and may facilitate both early onset and aggressive tumor growth while inhibiting anti-tumorigenic properties. The TME of AA patients often exhibits an immunosuppressive microenvironment with a substantial enrichment of immune inflammatory pathways and genes. As a result, AA patients can potentially benefit more from treatment strategies that modulate the immune system. Focusing on TME components for diagnostic and therapeutic purposes to address racial disparities is a promising area of investigation. Future basic and clinical research studies on personalized cancer diagnosis and treatment should acknowledge the significance of TME in racial disparities.

scholarly journals In Vivo Fluorescence Imaging and Urinary Monoamines as Surrogate Biomarkers of Disease Progression in a Mouse Model of Pheochromocytoma

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4149-4156 ◽  
Author(s):  
Martin Ullrich ◽  
Ralf Bergmann ◽  
Mirko Peitzsch ◽  
Marc Cartellieri ◽  
Nan Qin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Fluorescence Imaging ◽  
Fluorescence Intensity ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Small Animal ◽  
Whole Body

Abstract Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine-producing chromaffin cells. Especially for metastatic PHEO, the availability of animal models is essential for developing novel therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable quantification of multiple organ lesions depends on dedicated small-animal in vivo imaging, which is still challenging and only available at specialized research facilities. Here, we investigated whether whole-body fluorescence imaging and monitoring of urinary free monoamines provide suitable parameters for measuring tumor progression in a murine allograft model of PHEO. We generated an mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells were injected subcutaneously into nude mice to perform whole-body fluorescence imaging of tumor development. Urinary free monoamines were measured by liquid chromatography with tandem mass spectrometry. Tumor fluorescence intensity and urinary outputs of monoamines showed tumor growth–dependent increases (P < .001) over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic blood pressure was increased significantly during tumor growth. Tumor volume correlated significantly (P < .001) and strongly with tumor fluorescence intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952), methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine (rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of lesions at diameters below 2.3 mm. Our results demonstrate that mouse pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines provide precise parameters of tumor progression in this sc mouse model of PHEO. This animal model will allow for testing new treatment strategies for chromaffin cell tumors.

scholarly journals Preclinical and Clinical Therapeutic Strategies Affecting Tumor-Associated Macrophages in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
H. Degroote ◽  
A. Van Dierendonck ◽  
A. Geerts ◽  
H. Van Vlierberghe ◽  
L. Devisscher
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Underlying Liver Disease ◽  
Promote Tumor Growth ◽  
Promising Target ◽  
Anticancer Immunity ◽  
Stimulation Of

Hepatocellular carcinoma (HCC) most often develops in patients with underlying liver disease characterized by chronic nonresolving inflammation. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations within the tumoral microenvironment. As key actors of cancer-related inflammation, they promote tumor growth by suppression of effective anticancer immunity, stimulation of angiogenesis, and tissue remodeling. Therefore, they have become an attractive and promising target for immunotherapy. The heterogeneity of TAM subtypes and their origin and dynamic phenotype during the initiation and progression of HCC has been partially unraveled and forms the base for the development of therapeutic agents. Current approaches are aimed at decreasing the population of TAMs by depleting macrophages present in the tumor, blocking the recruitment of bone marrow-derived monocytes, and/or functionally reprogramming TAMs to antitumoral behavior. In this review, the preclinical evolution and hitherto clinical trials for TAM-targeted therapy in HCC will be highlighted.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 265
Author(s):  
Maria-Luisa Pérez-Lozano ◽  
Annabelle Cesaro ◽  
Marija Mazor ◽  
Eric Esteve ◽  
Sabine Berteina-Raboin ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Natural Product ◽  
Treatment Strategies ◽  
Cartilage Degradation ◽  
Therapeutic Strategies ◽  
Clinical Models ◽  
Osteoarthritic Joint ◽  
Dietary Components ◽  
New Treatment ◽  
Review Current

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment. In the present review, we provide an overview of current and emerging natural-product-based research treatments for OA management by drawing attention to experimental, pre-clinical, and clinical models. Herein, we review current and emerging natural-product-based research treatments for OA management.

scholarly journals Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 903
Author(s):  
Xiao-Mei Zhang ◽  
De-Gao Chen ◽  
Shengwen Calvin Li ◽  
Bo Zhu ◽  
Zhong-Jun Li
Keyword(s):  
Metabolic Regulation ◽  
Transcriptional Profiling ◽  
Tumor Development ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Functional Heterogeneity ◽  
Tumor Associated Macrophages ◽  
Metabolic Remodeling ◽  
And Function ◽  
Mapping Models

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous “camouflage” in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages’ ontogeny in macrophages’ functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs’ origins may help understand the classification of TAMs’ population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies.

Tumor associated macrophages and neutrophils in tumor progression

2013 ◽  
Vol 228 (7) ◽  
pp. 1404-1412 ◽  
Author(s):  
Maria R. Galdiero ◽  
Cecilia Garlanda ◽  
Sébastien Jaillon ◽  
Gianni Marone ◽  
Alberto Mantovani
Keyword(s):  
Tumor Progression ◽  
Tumor Associated Macrophages
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