Mesenchymal Stem Cells in Gastric Cancer: Vicious but Hopeful.
TL;DR: In this paper, Mesenchymal stem cells (MSC) represent the decisive components of tumor stroma that are found to strongly affect GC development and progression, and they also engage in remodeling the stroma better suited for tumor progression through immunosuppression, pro-angiogenesis, as well as extracellular matrix reshaping.
Abstract: Tumor progression depends on the collaborative interactions between tumor cells and the surrounding stroma. First-line therapies direct against cancer cells may not reach a satisfactory outcome, such as gastric cancer (GC), with high risk of recurrence and metastasis. Therefore, novel treatments and drugs target the effects of stroma components are to be promising alternatives. Mesenchymal stem cells (MSC) represent the decisive components of tumor stroma that are found to strongly affect GC development and progression. MSC from bone marrow or adjacent normal tissues express homing profiles in timely response to GC-related inflammation signals and anchor into tumor bulks. Then the newly recruited "naive" MSC would achieve phenotype and functional alternations and adopt the greater tumor-supporting potential under the reprogramming of GC cells. Conversely, both new-comers and tumor-resident MSC are able to modulate the tumor biology via aberrant activation of oncogenic signals, metabolic reprogramming and epithelial-to-mesenchymal transition. And they also engage in remodeling the stroma better suited for tumor progression through immunosuppression, pro-angiogenesis, as well as extracellular matrix reshaping. On the account of tumor tropism, MSC could be engineered to assist earlier diagnosis of GC and deliver tumor-killing agents precisely to the tumor microenvironment. Meanwhile, intercepting and abrogating vicious signals derived from MSC are of certain significance for the combat of GC. In this review, we mainly summarize current advances concerning the reciprocal metabolic interactions between MSC and GC and their underlying therapeutic implications in the future.
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TL;DR: In this article, the authors discuss the prospects of MSC-associated anticancer strategies in light of therapeutic mechanisms and signal transduction pathways and assess the clinical trials designed to appraise the efficacy and safety of mesenchymal stem/stromal cells-based anticancer therapies according to published data.
Abstract: The multipotent mesenchymal stem/stromal cells (MSCs), initially discovered from bone marrow in 1976, have been identified in nearly all tissues of human body now. The multipotency of MSCs allows them to give rise to osteocytes, chondrocytes, adipocytes, and other lineages. Moreover, armed with the immunomodulation capacity and tumor-homing property, MSCs are of special relevance for cell-based therapies in the treatment of cancer. However, hampered by lack of knowledge about the controversial roles that MSC plays in the crosstalk with tumors, limited progress has been made with regard to translational medicine. Therefore, in this review, we discuss the prospects of MSC-associated anticancer strategies in light of therapeutic mechanisms and signal transduction pathways. In addition, the clinical trials designed to appraise the efficacy and safety of MSC-based anticancer therapies will be assessed according to published data.
46 citations
TL;DR: In this article, the authors provide an overview of bidirectional interactions between cancer stem cells and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis.
Abstract: Cross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (Treg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.
15 citations
TL;DR: In this paper, the interplay between Helicobacter pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs), was discussed.
12 citations
TL;DR: An overview of the association of the factors playing a role in chronic inflammation; the bacterial characteristics which are responsible for the colonization, persistence in the stomach, and triggering ofinflammatory; the microbiome involved in the chronic inflammation process; and the host factors that have arole in determining whether gastritis progresses to gastric cancer are provided.
Abstract: Gastric cancer remains a major killer globally, although its incidence has declined over the past century. It is the fifth most common cancer and the third most common reason for cancer-related deaths worldwide. Gastric cancer is the outcome of a complex interaction between environmental, host genetic, and microbial factors. There is significant evidence supporting the association between chronic inflammation and the onset of cancer. This association is particularly robust for gastrointestinal cancers in which microbial pathogens are responsible for the chronic inflammation that can be a triggering factor for the onset of those cancers. Helicobacter pylori is the most prominent example since it is the most widespread infection, affecting nearly half of the world’s population. It is well-known to be responsible for inducing chronic gastric inflammation progressing to atrophy, metaplasia, dysplasia, and eventually, gastric cancer. This review provides an overview of the association of the factors playing a role in chronic inflammation; the bacterial characteristics which are responsible for the colonization, persistence in the stomach, and triggering of inflammation; the microbiome involved in the chronic inflammation process; and the host factors that have a role in determining whether gastritis progresses to gastric cancer. Understanding these interconnections may improve our ability to prevent gastric cancer development and enhance our understanding of existing cases.
8 citations
TL;DR: In this article , the role of metabolic reprogramming mediated BM-MSC education by gastric cancer (GC) cells was revealed. But, whether metabolic re-rogramming mediates transformation of BM-derived mesenchymal stem cells remains elusive.
Abstract: Tumor microenvironment and metabolic reprogramming are critical for tumor metastasis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely involved in the formation of tumor microenvironment and present oncogenic phenotypes to facilitate lymph node metastasis (LNM) in response to small extracellular vesicles (sEV) released by gastric cancer (GC) cells. However, whether metabolic reprograming mediates transformation of BM-MSCs remains elusive. Herein, we revealed that the capacity of LNM-GC-sEV educating BM-MSCs was positively correlated with the LNM capacity of GC cells themselves. Fatty acid oxidation (FAO) metabolic reprogramming was indispensable for this process. Mechanistically, CD44 was identified as a critical cargo for LNM-GC-sEV enhancing FAO via ERK/PPARγ/CPT1A signaling. ATP was shown to activate STAT3 and NF-κB signaling to induce IL-8 and STC1 secretion by BM-MSCs, thereby in turn facilitating GC cells metastasis and increasing CD44 levels in GC cells and sEV to form a persistent positive feedback loop between GC cells and BM-MSCs. The critical molecules were abnormally expressed in GC tissues, sera and stroma, and correlated with the prognosis and LNM of GC patients. Together, our findings uncover the role of metabolic reprogramming mediated BM-MSCs education by LNM-GC-sEV, which presents a novel insight into the mechanism underlying LNM and provides candidate targets for GC detection and therapy.
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Abstract: This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions There will be an estimated 181 million new cancer cases (170 million excluding nonmelanoma skin cancer) and 96 million cancer deaths (95 million excluding nonmelanoma skin cancer) in 2018 In both sexes combined, lung cancer is the most commonly diagnosed cancer (116% of the total cases) and the leading cause of cancer death (184% of the total cancer deaths), closely followed by female breast cancer (116%), prostate cancer (71%), and colorectal cancer (61%) for incidence and colorectal cancer (92%), stomach cancer (82%), and liver cancer (82%) for mortality Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality) Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts CA: A Cancer Journal for Clinicians 2018;0:1-31 © 2018 American Cancer Society
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TL;DR: The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC, believing this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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TL;DR: Tumors of epithelioma are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.
Abstract: SOLID tumors are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.1 , 2 In tumors of epitheli...
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TL;DR: The linear increase in the number of colonies with increasing numbers of explanted cells and the distribution of male and female cells in mixed cultures support the view that fibroblast colonies are clones.
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