Role of interleukin-6 in cancer progression and therapeutic resistance

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity.

Download Full-text

Targeting Tumor-derived exosomes expressing CD73: new opportunities in the pathogenesis and treatment of cancer

Current Molecular Medicine ◽

10.2174/1566524020666201120142953 ◽

2020 ◽

Vol 20 ◽

Author(s):

Vajihe Taghdiri Nooshabadi ◽

Samaneh Arab

Keyword(s):

Tumor Microenvironment ◽

Cancer Progression ◽

Cancer Development ◽

Therapeutic Resistance ◽

Intracellular Communication ◽

Different Types ◽

Therapeutic Protocols ◽

Tumor Exosomes ◽

Selection Of

: Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cellderived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer.

Download Full-text

A Potential Role of IL-6/IL-6R in the Development and Management of Colon Cancer

Membranes ◽

10.3390/membranes11050312 ◽

2021 ◽

Vol 11 (5) ◽

pp. 312

Author(s):

Mimmo Turano ◽

Francesca Cammarota ◽

Francesca Duraturo ◽

Paola Izzo ◽

Marina De Rosa

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Progression ◽

Interleukin 6 ◽

Potential Role ◽

Target Cells ◽

Sporadic Colorectal Cancer ◽

Colon Cancer Progression ◽

Interleukin 6 Receptor

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second greatest cause of cancer deaths. About 75% of all CRCs are sporadic cancers and arise following somatic mutations, while about 10% are hereditary cancers caused by germline mutations in specific genes. Several factors, such as growth factors, cytokines, and genetic or epigenetic alterations in specific oncogenes or tumor-suppressor genes, play a role during the adenoma–carcinoma sequence. Recent studies have reported an increase in interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels in the sera of patients affected by colon cancer that correlate with the tumor size, suggesting a potential role for IL-6 in colon cancer progression. IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles. Two different types of IL-6 signaling are known. Classic IL-6 signaling involves the binding of IL-6 to its membrane receptor on the surfaces of target cells; alternatively, IL-6 binds to sIL-6R in a process called IL-6 trans-signaling. The activation of IL-6 trans-signaling by metalloproteinases has been described during colon cancer progression and metastasis, involving a shift from membrane-bound interleukin-6 receptor (IL-6R) expression on the tumor cell surface toward the release of soluble IL-6R. In this review, we aim to shed light on the role of IL-6 signaling pathway alterations in sporadic colorectal cancer and the development of familial polyposis syndrome. Furthermore, we evaluate the possible roles of IL-6 and IL-6R as biomarkers useful in disease follow-up and as potential targets for therapy, such as monoclonal antibodies against IL-6 or IL-6R, or a food-based approach against IL-6.

Download Full-text

Glutathione metabolism in cancer progression and treatment resistance

The Journal of Cell Biology ◽

10.1083/jcb.201804161 ◽

2018 ◽

Vol 217 (7) ◽

pp. 2291-2298 ◽

Cited By ~ 152

Author(s):

Ankita Bansal ◽

M. Celeste Simon

Keyword(s):

Cancer Progression ◽

Treatment Options ◽

Redox Homeostasis ◽

Treatment Resistance ◽

Glutathione Metabolism ◽

Therapeutic Resistance ◽

Cellular Redox ◽

Gsh Metabolism ◽

Living Organisms

Glutathione (GSH) is the most abundant antioxidant found in living organisms and has multiple functions, most of which maintain cellular redox homeostasis. GSH preserves sufficient levels of cysteine and detoxifies xenobiotics while also conferring therapeutic resistance to cancer cells. However, GSH metabolism plays both beneficial and pathogenic roles in a variety of malignancies. It is crucial to the removal and detoxification of carcinogens, and alterations in this pathway can have a profound effect on cell survival. Excess GSH promotes tumor progression, where elevated levels correlate with increased metastasis. In this review, we discuss recent studies that focus on deciphering the role of GSH in tumor initiation and progression as well as mechanisms underlying how GSH imparts treatment resistance to growing cancers. Targeting GSH synthesis/utilization therefore represents a potential means of rendering tumor cells more susceptible to different treatment options such as chemotherapy and radiotherapy.

Download Full-text