Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity

Saxena, Sugandha; Singh, Rakesh K.

doi:10.1007/s10555-021-09970-6

Cited by 30 publications

(15 citation statements)

References 445 publications

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“…This represents a significant challenge in CSC research, due to their nature as cells with uncontrolled proliferation activity and self-renewal ability, thus making it hard to target the tumor. Consequently, CSCs and all undifferentiated cells within a tumor may develop these properties, depending on the cell’s environmental context or under appropriate stimuli [ 35 , 81 , 82 ]. Undeniably, the tumor microenvironment plays a predominant role in this cell transformation, and provides a niche where the newly formed CSCs have all the necessary supplies for their growth and maintenance [ 43 ].…”

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

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Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

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Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

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“…Chemokines exert their biological effects through interactions with G-protein linked transmembrane receptors (chemokine receptors) and participate in the proliferation, invasion, and metastasis of tumor cells [ 12 ]. Among them, CXC-motif chemokine ligand (CXCL) family is involved in regulating immune cell activity, inducing tumor cell migration, and regulating tumor cell proliferation and neoplastic microvascular formation, which is closely related to tumor occurrence and development [ 13 , 14 ]. CXCL family contains CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, and CXCL17, involved in the invasion and metastasis of gastric cancer [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Prognostic Values of CXCL Family in Epstein–Barr Virus Associated Gastric Cancer

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. CXCL family is a class of secreted growth factors signaling through G-protein-coupled receptors, and abnormal expression is associated with the growth and progression of many tumors. However, their prognostic value has been poorly studied in Epstein–Barr virus- (EBV-) associated gastric cancer (EBVaGC). Therefore, it is of great significance to explore the prognostic value of the CXCL family in EBVaGC. Methods. CXCL family mRNA expression was analyzed in STAD data from The Cancer Genome Atlas (TCGA). Kaplan-Meier Plotter was used to assess the prognostic value of the CXCL family. Transcription factors (TFs) and miRNAs associated with the CXCL family were identified by TFCheckpoint, miRWalk, and ViRBase databases. The prognostic model was evaluated using the EBVaGC patient cohort GSE51575. Results. The mRNA expression of CXCL1/3/5/6/8/9/10/11/16 was significantly upregulated, while the expression of CXCL12/14 was downregulated in EBVaGC compared with normal tissues from TCGA-STAD. The mRNA expressions of CXCL9, CXCL10, CXCL11, and CXCL17 in EBVaGCs were higher than those in EBVnGCs, but the mRNA expressions of CXCL6, CXCL12, and CXCL17 were lower than those in EBVnGCs. The mRNA expression levels of CXCL9, CXCL10, and CXCL11 in EBVaGCs were higher than those in EBVnGCs regardless of the tumor stage. High mRNA expression of CXCL8 was associated with better OS in patients with EBVaGC, while high expression of CXCL9 was associated with better OS in patients with EBVnGC. We obtained 10 candidate potential transcription factors (TFs) associated with CXCLs: OTOP3, NKX6-2, NKX2-2, FEV, SMYD1, TRIMSO, TBX10, CDX1, SLC26A3, and ARC. 576 miRNA-mRNA interactions were obtained. Among them, 65 miRNAs were predicted to be correlated with CXCL6, CXCL9, CXCL10, and CXCL11. Similar to the results of TCGA-STAD, the GSE51575 dataset also showed that the mRNA expression levels of CXCL1/3/9/10/11/16 were markedly enhanced in EBVaGC tissues compared with corresponding normal gastric mucosa tissues, while the mRNA expression levels of CXCL12/14 were significantly reduced. The mRNA expression levels of CXCL3/9/10/11/13/17 were increased in EBVaGC compared with EBVnGC tissues. Conclusions. The expression differences of CXCL family members are closely associated with the progression of EBVaGC. Expression of CXCL9/10/11/17 mRNA may be a promising prognostic indicator for EBVaGC patients.

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“…Secondly, cancer stem cells, a subset of self-renewing cancer cells that are able to initiate tumour growth, may play an important role in resistance to therapy [ 136 ]. Although under-researched, the role of chemokines in the maintenance and positioning of these cells may unearth new targets for inhibiting the tumorigenic functions of these cells [ 137 ]. In addition, melanoma is the most immunogenic tumour and appears to be reliant on the recruitment of immune cells for its progression, and yet, it appears to be a cancer with the fewest clinical studies of chemokine manipulation.…”

Section: Discussion: Challenges In Studying Of Chemokine Network and Implications For Clinical Translationmentioning

confidence: 99%

Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician

Adams

Moser

Karagiannis

et al. 2021

Cancers

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The incidence of cutaneous malignant melanoma is rising globally and is projected to continue to rise. Advances in immunotherapy over the last decade have demonstrated that manipulation of the immune cell compartment of tumours is a valuable weapon in the arsenal against cancer; however, limitations to treatment still exist. Cutaneous melanoma lesions feature a dense cell infiltrate, coordinated by chemokines, which control the positioning of all immune cells. Melanomas are able to use chemokine pathways to preferentially recruit cells, which aid their growth, survival, invasion and metastasis, and which enhance their ability to evade anticancer immune responses. Aside from this, chemokine signalling can directly influence angiogenesis, invasion, lymph node, and distal metastases, including epithelial to mesenchymal transition-like processes and transendothelial migration. Understanding the interplay of chemokines, cancer cells, and immune cells may uncover future avenues for melanoma therapy, namely: identifying biomarkers for patient stratification, augmenting the effect of current and emerging therapies, and designing specific treatments to target chemokine pathways, with the aim to reduce melanoma pathogenicity, metastatic potential, and enhance immune cell-mediated cancer killing. The chemokine network may provide selective and specific targets that, if included in current therapeutic regimens, harbour potential to improve outcomes for patients.

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Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity

Cited by 30 publications

References 445 publications

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Characterization of the Prognostic Values of CXCL Family in Epstein–Barr Virus Associated Gastric Cancer

Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician

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