Interplay between inflammatory tumor microenvironment and cancer stem cells (Review)

Zhang, Shijian; Yang, Xi; Wang, Lei; Zhang, Chenping

doi:10.3892/ol.2018.8716

Cited by 53 publications

(54 citation statements)

References 93 publications

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“…Tumor microenvironment is usually characterized by an abnormal release of proinflammatory cytokines, which plays an important role in cancer metastasis [17]. Of the important cytokines involved in this process, interleukin 6 (IL -6) have been linked with induction of drug resistance, stem cell like characteristics and EMT induced metastasis in breast cancer [18] [19] [20]. Interestingly, few number of breast cancer studies have suggested that YBX-1 interacts with IL-6 creating a positive feed-forward loop driving EMT-like metastatic properties during cancer progression [21].…”

Section: Introductionmentioning

confidence: 99%

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Abd-Elaziz¹,

Moneim²,

Fek³

et al. 2019

ABCR

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Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients' records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p < 0.001) and IL-6 (p < 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (r s = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.

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Section: Introductionmentioning

confidence: 99%

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Abd-Elaziz¹,

Moneim²,

Fek³

et al. 2019

ABCR

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“…Recent studies [117,118] suggest that JNK signaling also plays a role in forming the CSC niche and regulating crosstalk within the niche. JNK signaling also regulates the CSC niche through inflammatory cells, which play central roles in initiation, proliferation, and metastasis of tumors [119].…”

Section: Crosstalk Between the Tumor Microenvironment And Cancer Stemmentioning

confidence: 99%

JNK Signaling in Stem Cell Self-Renewal and Differentiation

Semba

Sammons

Wang

et al. 2020

IJMS

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C-JUN N-terminal kinases (JNKs), which belong to the mitogen-activated protein kinase (MAPK) family, are evolutionarily conserved kinases that mediate cell responses to various types of extracellular stress insults. They regulate physiological processes such as embryonic development and tissue regeneration, playing roles in cell proliferation and programmed cell death. JNK signaling is also involved in tumorigenesis and progression of several types of malignancies. Recent studies have shown that JNK signaling has crucial roles in regulating the traits of cancer stem cells (CSCs). Here we describe the functions of the JNK signaling pathway in self-renewal and differentiation, which are essential features of various types of stem cells, such as embryonic, induced pluripotent, and adult tissue-specific stem cells. We also review current knowledge of JNK signaling in CSCs and discuss its role in maintaining the CSC phenotype. A better understanding of JNK signaling as an essential regulator of stemness may provide a basis for the development of regenerative medicine and new therapeutic strategies against malignant tumors.

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“…Oral Cancers include many squamous cell carcinomas that may have varying responsiveness to chemotherapy and radiation treatments [1,2]. Recent evidence has demonstrated that a sub-population of oral cancers may be cancer stem cells (CSC), which exhibit cancerous but also stem cell phenotypesincluding chemotherapeutic and radiation resistance [3,4]. Based upon these phenotypes, recent efforts have focused on identifying specific biomarkers to identify tumors with sub-populations of CSC [5,6].…”

Section: Introductionmentioning

confidence: 99%

Differential exosome miRNA expression in oral cancer stem cells

Shoff

Booker

Leavitt

et al. 2020

ExRNA

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Background: Oral squamous cell carcinomas (OSCC) secrete exosomes into the surrounding extracellular environment to promote the horizontal transfer of bioactive molecules including microRNA (miRNA). The primary objective of this study was to explore potential differences in miRNA content between OSCC and OSCC stem cells.Methods: The OSCC cell lines SCC4, SCC15, SCC25 and CAL27 were used in these studies. The corresponding OSCC stem cells that demonstrated phenotypic adhesion independent tumor spheres (AiTS) were manually isolated. All cells were cultured in DMEM containing 10% exosome-free fetal bovine serum. Exosomes were isolated using Total Exosome Isolation reagent (Invitrogen) and RNA was purified using Total Exosome RNA isolation kit (Invitrogen). Exosome miRNA content was evaluated using miRNA Advanced Taqman Assays for miR-21, − 155, − 133, − 34, − 31, − 32, and − 365. The fold change of miRNA content was calculated using the comparative CT (ΔΔCT) method using miR-16 as an endogenous control. Results: After successful cell cultures were established, AiTS (cancer stem cells) were manually separated and confirmed using CD133 and Sox-2 biomarkers. Exosomes and extracellular vesicles were successfully isolated from all cell lines and AiTS isolates for miRNA screening. All isolates exhibited miR-16 expression (positive control), but none contained mir-31, − 32, or 133a. Differential expression of miR-21, miR-34 and miR-155 were observed with patterns observed among the cancer cell lines which were distinct from the corresponding AiTS isolates. Conclusions: Exosomes isolated from these different OSCC stem cell populations displayed nearly consistent downregulation/loss of miR-21 and miR-34 suggesting the possibility of a unique miRNA profile characteristic of oral cancer stem cells. These findings highlight the need to investigate the comprehensive functions of miR-21 and miR-34 in tumor progression and continued research to refine a miRNA profile that could aid in distinguishing tumors with poor prognosis.

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Interplay between inflammatory tumor microenvironment and cancer stem cells (Review)

Cited by 53 publications

References 93 publications

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

JNK Signaling in Stem Cell Self-Renewal and Differentiation

Differential exosome miRNA expression in oral cancer stem cells

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