scholarly journals CC Chemokine Receptor 5: The Interface of Host Immunity and Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Carlos Eduardo Coral de Oliveira ◽  
Julie Massayo Maeda Oda ◽  
Roberta Losi Guembarovski ◽  
Karen Brajão de Oliveira ◽  
Carolina Batista Ariza ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Malignant Tumors ◽  
Host Immunity ◽  
Immune Defense ◽  
Cellular Migration ◽  
Ccr5 Chemokine Receptor ◽  
Stromal Microenvironment ◽  
Promote Tumor Growth

Solid tumors are embedded in a stromal microenvironment consisting of immune cells, such as macrophages and lymphocytes, as well as nonimmune cells, such as endothelial cells and fibroblasts. Chemokines are a type of small secreted chemotactic cytokine and together with their receptors play key roles in the immune defense. Critically, they regulate cancer cellular migration and also contribute to their proliferation and survival. The CCR5 chemokine receptor is involved in leucocytes chemotaxis to sites of inflammation and plays an important role in the macrophages, T cells, and monocytes recruitment. Additionally, CCR5 may have an indirect effect on cancer progression by controlling the antitumor immune response, since it has been demonstrated that its expression could promote tumor growth and contribute to tumor metastasis, in different types of malignant tumors. Furthermore, it was demonstrated that a CCR5 antagonist may inhibit tumor growth, consisting of a possible therapeutic target. In this context, the present review focuses on the establishment of CCR5 within the interface of host immunity, tumor microenvironment, and its potential as a targeting to immunotherapy.

scholarly journals Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p

2021 ◽  
Vol 11 ◽  
Author(s):  
Chung-Hsien Shih ◽  
Li-Ling Chuang ◽  
Mong-Hsun Tsai ◽  
Li-Han Chen ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cellular Migration ◽  
Expression Levels ◽  
Promote Tumor Growth ◽  
Rna Immunoprecipitation ◽  
And Migration

Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.

scholarly journals Independence of HIF1a and androgen signaling pathways in prostate cancer

2019 ◽  
Author(s):  
Maxine GB Tran ◽  
Becky AS Bibby ◽  
Lingjian Yang ◽  
Franklin Lo ◽  
Anne Warren ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Promote Tumor Growth ◽  
Elevated Expression

AbstractAndrogen signaling drives prostate cancer progression and is a therapeutic target. Hypoxia/HIF1a signaling is associated with resistance to hormone therapy and a poor prognosis in patients treated with surgery or radiotherapy. It is not known whether the pathways operate in cooperation or independently. Using LNCaP cells with and without stable transfection of a HIF1a expression vector, we show that combined AR and HIF1a signaling promotes tumor growth in vitro and in vivo, and the capacity of HIF1a to promote tumor growth in the absence of endogenous androgen in vivo. Gene expression analysis identified 7 genes that were upregulated by both androgen and HIF1a. ChIP-Seq analysis showed that the AR and HIF/hypoxia signaling pathways function independently regulating the transcription of different genes with few shared targets. In clinical datasets elevated expression of 5 of the 7 genes was associated with a poor prognosis. Our findings suggest that simultaneous therapeutic inhibition of AR and HIF1a signaling pathways should be explored as a potential therapeutic strategy.

scholarly journals Breast Cancer: An Examination of the Potential of ACKR3 to Modify the Response of CXCR4 to CXCL12

2018 ◽  
Vol 19 (11) ◽  
pp. 3592 ◽  
Author(s):  
Irene del Molino del Barrio ◽  
Georgina Wilkins ◽  
Annette Meeson ◽  
Simi Ali ◽  
John Kirby
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Chinese Hamster ◽  
Cellular Migration ◽  
Receptor Internalization ◽  
Calcium Flux ◽  
Akt Phosphorylation ◽  
Erk Phosphorylation ◽  
Chemokine Cxcl12

Upon binding with the chemokine CXCL12, the chemokine receptor CXCR4 has been shown to promote breast cancer progression. This process, however, can be affected by the expression of the atypical chemokine receptor ACKR3. Given ACKR3’s ability to form heterodimers with CXCR4, we investigated how dual expression of both receptors differed from their lone expression in terms of their signalling pathways. We created single and double CXCR4 and/or ACKR3 Chinese hamster ovary (CHO) cell transfectants. ERK and Akt phosphorylation after CXCL12 stimulation was assessed and correlated with receptor internalization. Functional consequences in cell migration and proliferation were determined through wound healing assays and calcium flux. Initial experiments showed that CXCR4 and ACKR3 were upregulated in primary breast cancer and that CXCR4 and ACKR3 could form heterodimers in transfected CHO cells. This co-expression modified CXCR4’s Akt activation after CXCL12’s stimulation but not ERK phosphorylation (p < 0.05). To assess this signalling disparity, receptor internalization was assessed and it was observed that ACKR3 was recycled to the surface whilst CXCR4 was degraded (p < 0.01), a process that could be partially inhibited with a proteasome inhibitor (p < 0.01). Internalization was also assessed with the ACKR3 agonist VUF11207, which caused both CXCR4 and ACKR3 to be degraded after internalization (p < 0.05 and p < 0.001), highlighting its potential as a dual targeting drug. Interestingly, we observed that CXCR4 but not ACKR3, activated calcium flux after CXCL12 stimulation (p < 0.05) and its co-expression could increase cellular migration (p < 0.01). These findings suggest that both receptors can signal through ERK and Akt pathways but co-expression can alter their kinetics and internalization pathways.

scholarly journals The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Dragana Nikitovic ◽  
Katerina Kouvidi ◽  
Nikos K. Karamanos ◽  
George N. Tzanakakis
Keyword(s):  
Cancer Progression ◽  
Malignant Tumors ◽  
Receptor Expression ◽  
Mesenchymal Tumors ◽  
Surface Receptors ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Promote Tumor Growth ◽  
Fibrosarcoma Cells ◽  
Tumor Types

Fibrosarcomas are rare malignant mesenchymal tumors originating from fibroblasts. Importantly, fibrosarcoma cells were shown to have a high content and turnover of extracellular matrix (ECM) components including hyaluronan (HA), proteoglycans, collagens, fibronectin, and laminin. ECMs are complicated structures that surround and support cells within tissues. During cancer progression, significant changes can be observed in the structural and mechanical properties of the ECM components. Importantly, hyaluronan deposition is usually higher in malignant tumors as compared to benign tissues, predicting tumor progression in some tumor types. Furthermore, activated stromal cells are able to produce tissue structure rich in hyaluronan in order to promote tumor growth. Key biological roles of HA result from its interactions with its specific CD44 and RHAMM (receptor for HA-mediated motility) cell-surface receptors. HA-receptor downstream signaling pathways regulate in turn cellular processes implicated in tumorigenesis. Growth factors, including PDGF-BB, TGFβ2, and FGF-2, enhanced hyaluronan deposition to ECM and modulated HA-receptor expression in fibrosarcoma cells. Indeed, FGF-2 through upregulation of specific HAS isoforms and hyaluronan synthesis regulated secretion and net hyaluronan deposition to the fibrosarcoma pericellular matrix modulating these cells’ migration capability. In this paper we discuss the involvement of hyaluronan/RHAMM/CD44 mediated signaling in the insidious pathways of fibrosarcoma progression.

scholarly journals Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1170
Author(s):  
Mithunah Krishnamoorthy ◽  
Lara Gerhardt ◽  
Saman Maleki Maleki Vareki
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Suppressor Cells ◽  
T Cell Immunity ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Immunity ◽  
Promote Tumor Growth

The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies.

scholarly journals JNK and Yorkie drive tumor malignancy by inducing L-amino acid transporter 1 in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009893
Author(s):  
Bojie Cong ◽  
Mai Nakamura ◽  
Yukari Sando ◽  
Takefumi Kondo ◽  
Shizue Ohsawa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Genetic Model ◽  
Malignant Tumors ◽  
Amino Acid Transporter ◽  
Rnai Screen ◽  
Oncogenic Mutations ◽  
Acid Transporter

Identifying a common oncogenesis pathway among tumors with different oncogenic mutations is critical for developing anti-cancer strategies. Here, we performed transcriptome analyses on two different models of Drosophila malignant tumors caused by Ras activation with cell polarity defects (RasV12/scrib-/-) or by microRNA bantam overexpression with endocytic defects (bantam/rab5-/-), followed by an RNAi screen for genes commonly essential for tumor growth and malignancy. We identified that Juvenile hormone Inducible-21 (JhI-21), a Drosophila homolog of the L-amino acid transporter 1 (LAT1), is upregulated in these malignant tumors with different oncogenic mutations and knocking down of JhI-21 strongly blocked their growth and invasion. JhI-21 expression was induced by simultaneous activation of c-Jun N-terminal kinase (JNK) and Yorkie (Yki) in these tumors and thereby contributed to tumor growth and progression by activating the mTOR-S6 pathway. Pharmacological inhibition of LAT1 activity in Drosophila larvae significantly suppressed growth of RasV12/scrib-/- tumors. Intriguingly, LAT1 inhibitory drugs did not suppress growth of bantam/rab5-/- tumors and overexpression of bantam rendered RasV12/scrib-/- tumors unresponsive to LAT1 inhibitors. Further analyses with RNA sequencing of bantam-expressing clones followed by an RNAi screen suggested that bantam induces drug resistance against LAT1 inhibitors via downregulation of the TMEM135-like gene CG31157. Our observations unveil an evolutionarily conserved role of LAT1 induction in driving Drosophila tumor malignancy and provide a powerful genetic model for studying cancer progression and drug resistance.

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