Colorectal cancer stem cells properties and features: evidence of interleukin-8 involvement

Abstract

Colorectal cancer (CRC) still remains a disease with high percentage of death, principally due to therapy resistance and metastasis. During the time the hypothesis has been reinforced that CRC stem cells (CRCSC) are involved in allowing intratumoral heterogeneity, drug escape mechanisms and secondary tumors. CRCSC are characterized by specific surface markers (i.e., CD44 and CD133), signaling pathways activation (i.e., Wnt and Notch) and gene expression (i.e., Oct4 and Snail), which confer to CRCSC self-renewal abilities and pluripotent capacity. Interleukin (IL)-8 is correlated to CRC progression, development of liver metastases and chemoresistance; moreover, IL-8 modulates not only stemness maintenance but also stemness promotion, such as epithelial-mesenchymal transition. This review wants to give a brief and up-to-date overview on IL-8 implication in CRCSC cues.

Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker

“…Tumor-derived IL-8 displays autocrine activities, sustaining CRC tumorigenesis and treatment resistance. IL-8 maintains and promotes cell stemness through Snail-dependent EMT, among other mechanisms ( Figure 1 B) [ 10 ]. On the other hand, Oct4, a specific marker of CRC stem cells, promotes IL-8 upregulation [ 24 ].…”

“…Among the canonical effects caused by tumor-derived IL-8, VEGF-independent angiogenesis is one of most characterized; by binding CXCR1 and CXCR2 expressed by endothelial cells, soluble IL-8 induces endothelial cell proliferation and capillary tube organization [ 9 ]. IL-8 also contributes to the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSC) generation and maintenance; our group recently reviewed the molecular mechanisms by which IL-8 promotes stemness in the CRC niche [ 10 ]. On the other hand, immune cell populations also contribute to IL-8 production, both within the TME and systemically [ 8 ].…”

Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: Mechanisms and clinical implications

“…Previous studies have suggested that IL-8 is an inflammatory cytokine released from many types of cells, such as macrophages, stromal, endothelial, epithelial and tumor cells, involved in promoting EMT, angiogenesis, tumor growth, metastasis and the immunosuppressive microenvironment in human cancers including CRC (105)(106)(107)(108)(109)(110)(111)(112). Previous studies also revealed that a high expression level of IL-8 in human CRC tissues, mediated by IL-8 functional receptors IL-8RA and IL-8RB (43,110,(113)(114)(115), was particularly associated with the properties and features of CSCs (51,113). Recent studies have confirmed that IL-8 is an of the important modulators of the biological behavior of CSCs e.g., stemness properties that contribute to CRC recurrence and metastasis (42,(113)(114)(115)(116)(117).…”

“…Previous studies also revealed that a high expression level of IL-8 in human CRC tissues, mediated by IL-8 functional receptors IL-8RA and IL-8RB (43,110,(113)(114)(115), was particularly associated with the properties and features of CSCs (51,113). Recent studies have confirmed that IL-8 is an of the important modulators of the biological behavior of CSCs e.g., stemness properties that contribute to CRC recurrence and metastasis (42,(113)(114)(115)(116)(117). These regulatory effects were found to be mediated via a direct impact on the generation and maintenance of CSCs (42, 113-117) through its functional receptors IL-8RA and IL-8RB expressed in CSCs (43,110,(113)(114)(115).…”

“…Recent studies have confirmed that IL-8 is an of the important modulators of the biological behavior of CSCs e.g., stemness properties that contribute to CRC recurrence and metastasis (42,(113)(114)(115)(116)(117). These regulatory effects were found to be mediated via a direct impact on the generation and maintenance of CSCs (42, 113-117) through its functional receptors IL-8RA and IL-8RB expressed in CSCs (43,110,(113)(114)(115). A study by Hwang et al revealed that the stemness properties of CD44-positive CSCs in CRC were regulated by Snail-IL-8 axis.…”