scholarly journals M2 macrophage microvesicle-inspired nanovehicles improve accessibility to cancer cells and cancer stem cells in tumors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuqi Wang ◽  
Xiang Gong ◽  
Jie Li ◽  
Hong Wang ◽  
Xiaoxuan Xu ◽  
...  

AbstractCancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy. Graphical Abstract

Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora

: 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.


2021 ◽  
Author(s):  
Ningwei Fu ◽  
Ning Fan ◽  
Wenchao Luo ◽  
Lijia Lv ◽  
Jing Li ◽  
...  

Abstract Purpose: TFEB is a key regulator of autophagy-lysosomal biogenesis pathways, while its dysregulation is highly prevalent in various human cancers, but the specific contribution to breast cancer remains poorly understood. The main purpose of this study is to explore the role of TFEB in breast cancer proliferation, metastasis and maintaining breast cancer stem cells (BCSCs) traits, thus uncovering its underlying mechanism.Methods: Bioinformatics, western blotting and immunohistochemical staining were applied to analyze the expression of TFEB in breast cancer. Stable down-regulation TFEB cells were established in MCF-7 and MDA-MB-231 breast cancer cell lines. MTT, clone formation, wound healing, transwell and 3D tumor invasion assays were used to evaluate the proliferation, migration and invasion ability of breast cancer cells. Mammosphere formation, immunocytochemical (ICC) staining were used to detect the effect of down-regulating TFEB on breast cancer stem cells. Results: we demonstrated that higher expression of TFEB was found in breast cancer. TFEB depletion had inhibitory effects on cellular proliferation, migration and invasion of breast cancer cells. Moreover, knockdown TFEB decreased mammosphere formation ability of BCSCs and expression of cancer stem cell markers. Autophagy-lysosomal related proteins were decreased by down regulation of TFEB. Conclusion: we uncovered a critical role of TFEB in breast cancer proliferation and metastasis, and BCSCs self-renewal and stemness. The underlying mechanisms involve in maintaining BCSCs traits, and dysregulating lysosome functions.


Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.


2013 ◽  
Author(s):  
Seog-Young Kim ◽  
Jin W. Kang ◽  
Bokyoung Kim ◽  
Young D. Yoo ◽  
Yong T. Kwon ◽  
...  

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Muhammad Ali ◽  
Fatima Ali ◽  
Nadia Wajid

Since the cancer stem cells (CSC) have been identified in 1997 by Bonnet and Dick, more than 100,000 papers have been published on the CSC. Huge research on cancer stem cells helped the scientists to rethink about the cancer therapeutics as classic way of chemotherapy is ineffective because chemotherapy failed to kill these cells, the only reason of cancer relapse. The cancer theory of stem cells is one of the most trending theory in stem cells and cancer biology focusing on the understanding of biology of cancer cells for an enhanced and improved therapeutic approaches should be applied to cure the cancer. This mini-review is a short overview on the role of organ specific cancer stem cells in the organ specific cancer progression.


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 260 ◽  
Author(s):  
Donatella Lucchetti ◽  
Filomena Colella ◽  
Luigi Perelli ◽  
Claudio Ricciardi-Tenore ◽  
Federica Calapà ◽  
...  

Cancer cells secrete small extracellular vesicles (sEVs) that are involved in the remodeling of tumor microenvironment (TME) and can promote tumor progression. The role of sEVs and their molecular key players in colon cancer stem cells differentiation are poorly understood. This study aimed to analyze the role and content of sEVs released during the differentiation of colorectal cancer stem cells. Here we show that sEVs secretion during colon cancer stem cells differentiation is partially controlled by CD147, a well-known player involved in colon cancer tumorigenesis. CD147 + sEVs activate a signaling cascade in recipient cells inducing molecular invasive features in colon cancer cells. CD147 knockdown as well as anti-CD147 antibodies impaired sEVs release and downstream effects on recipient cells and blocking multivesicular body maturation prevented sEVs release during the differentiation. Our findings reveal a functional role of CD147 in promoting sEVs release during the differentiation of colon cancer stem cells and in triggering cellular changes in recipient cells.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12540-e12540
Author(s):  
Tae Hyun Kim ◽  
In-Sung Song ◽  
Jin Han

e12540 Background: Breast cancer is the most common non-skin cancer in women. Breast cancers are heterogeneous, and treatment by subgroup based on hormone receptor and HER2 made a significant difference in clinical outcomes. Several studies have reported that estrogen receptor beta (ERβ) decreases during tumor development in the breast epithelium. However, the role of ERβ in relapse and metastasis of breast cancer is poorly understood. Methods: In this study, we retrospectively studied 30 case breast carcinomas divided luminal, HER2, and triple negative subtype. Among them, patients relapsed within 5 years are 6 cases. The expression of ERβ gene in breast cancer tissues (30 cases) was estimated using a quantitative PCR, and other marker (ERα, HER2, PR etc) was measured anonymously in formalin-fixed paraffin-embedded tumor sections, by using specific antibodies. Results: A low level of ERβ expression and mitochondrial translocation of ERβ was associated with relapse/metastasis of breast cancer. The ERβ depletion resulted in resistance in response to tamoxifen treatment of MCF-7 breast cancer cells. Conversely, the overexpression of mitochondrial ERβ enhanced the cell death by treatment of tamoxifen in MCF-7 cells. We found that ERβ localizes to the mitochondria via the interaction with Grp75 and improves mitochondrial oxygen consumption rate and ATP production in breast cancer cells. Finally, we showed that ERβ level was a low in the breast cancer stem cells (CD24-CD44+ cells) compared with breast non-cancer stem cells (CD24+CD44- cells), whereas ERα level was a high. The overexpression of mitochondrial ERβ contribute to a decrease of sphere formation showing a tumorigenic ability. Conclusions: The mitochondrial ERβ contribute to suppress survival and stemness of cancer stem cells for relapse/metastasis, promising to the development of novel strategies for the treatment of breast cancer patients.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2839 ◽  
Author(s):  
Laetitia Delort ◽  
Lauriane Bougaret ◽  
Juliette Cholet ◽  
Marion Vermerie ◽  
Hermine Billard ◽  
...  

Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.


2019 ◽  
Vol 21 (1) ◽  
pp. 53 ◽  
Author(s):  
Saiprasad Gowrikumar ◽  
Amar B. Singh ◽  
Punita Dhawan

Claudins are cell–cell adhesion proteins, which are expressed in tight junctions (TJs), the most common apical cell-cell adhesion. Claudin proteins help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells. A series of studies have now reported dysregulation of claudin proteins in cancers. However, the precise mechanisms are still not well understood. Nonetheless, studies have clearly demonstrated a causal role of multiple claudins in the regulation of epithelial to mesenchymal transition (EMT), a key feature in the acquisition of a cancer stem cell phenotype in cancer cells. In addition, claudin proteins are known to modulate therapy resistance in cancer cells, a feature associated with cancer stem cells. In this review, we have focused primarily on highlighting the causal link between claudins, cancer stem cells, and therapy resistance. We have also contemplated the significance of claudins as novel targets in improving the efficacy of cancer therapy. Overall, this review provides a much-needed understanding of the emerging role of claudin proteins in cancer malignancy and therapeutic management.


2020 ◽  
Author(s):  
Rodrigo Peña-Hernández ◽  
Rossana Aprigliano ◽  
Sandra Frommel ◽  
Karolina Pietrzak ◽  
Seraina Steiger ◽  
...  

AbstractProstate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse and represent a target against metastatic PCa. Here we show that BAZ2A (also known as TIP5), a factor previously implicated in aggressive PCa, is required for the dedifferentiation of PCa cells into a cancer stem-like state. We found that BAZ2A genomic occupancy in PCa cells coincides with H3K14ac enriched chromatin regions. This association is mediated by BAZ2A bromodomain (BAZ2A-BRD) that specifically binds to H3K14ac. In PCa cells, BAZ2A-BRD is required for the interaction with a class of inactive enhancers that are marked by H3K14ac and represses transcription of genes implicated in developmental and differentiation processes that are frequently silenced in aggressive and dedifferentiated PCa. BAZ2A-mediated repression of these genes is also linked to the histone acetyltransferase EP300 that acetylates H3K14ac. Mutations of BAZ2A-BRD or treatment with chemical probes that abrogate BAZ2A-BRD association with H3K14ac impair the dedifferentiation of PCa cells into a stem-like state. Furthermore, pharmacological inactivation of BAZ2A-BRD impairs the oncogenic transformation mediated by Pten-loss in prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.


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