Role of Chemokines in Thyroid Cancer Microenvironment: Is CXCL8 the Main Player?

Abstract

Tumor-related inflammation does influence the biological behavior of neoplastic cells and ultimately the patient’s outcome. With specific regard to thyroid cancer, the issue of tumor-associated inflammation has been extensively studied and recently reviewed. However, the role of chemokines, which play a crucial role in determining the immuno-phenotype of tumor-related inflammation, was not addressed in previous reviews on the topic. Experimental evidence shows that thyroid cancer cells actively secrete a wide spectrum of chemokines and, at least for some of them, solid scientific data support a role for these immune-active molecules in the aggressive behavior of the tumor. Our proposal for a review article on chemokines and thyroid cancer stems from the notion that chemokines, besides having the ability to attract and maintain immune cells at the tumor site, also produce several pro-tumorigenic actions, which include proangiogenetic, cytoproliferative, and pro-metastatic effects. Studies taking into account the role of CCL15, C–X–C motif ligand 12, CXCL16, CXCL1, CCL20, and CCL2 in the context of thyroid cancer will be reviewed with particular emphasis on CXCL8. The reason for focusing on CXCL8 is that this chemokine is the most studied one in human malignancies, displaying multifaceted pro-tumorigenic effects. These include enhancement of tumor cells growth, metastatization, and angiogenesis overall contributing to the progression of several cancers including thyroid cancer. We aim at reviewing current knowledge on the (i) ability of both normal and tumor thyroid cells to secrete CXCL8; (ii) direct/indirect pro-tumorigenic effects of CXCL8 demonstrated by in vitro and in vivo studies specifically performed on thyroid cancer cells; and (iii) pharmacologic strategies proven to be effective for lowering CXCL8 secretion and/or its effects on thyroid cancer cells.

Interplay between thyroid cancer cells and macrophages: effects on IL-32 mediated cell death and thyroid cancer cell migration

“…We found that IL-32β overexpression in TPC-1 cells resulted in slightly less cell death, and a significant increase in IL-8 mRNA expression, whereas IL-32γ did not. IL-8 is an important pro-survival cytokine [26] and restoring the IL-8 signalling pathway has been found to rescue IL-32β-induced cell death in HEK293 cells [18]. Our results further showed that the expression of Ki-67, an important marker of proliferation, was slightly reduced after exogenous IL-32γ overexpression, suggesting a reduced proliferation potential.…”

Role of chemokine receptors in thyroid cancer and immunotherapy

“…CXCR2 binds the CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7 and CXCL8 chemokines. Among them, CXCL8 plays a major role in thyroid cancer microenvironment (Rotondi et al 2007(Rotondi et al , 2018. CXCR2 was described originally in leukocytes and subsequently in non-hematopoietic cells, such as keratinocytes, neurons and epidermal cells, in regions corresponding to intermediate levels of differentiation (Baggiolini et al 1989, Tecimer et al 2000, Waugh & Wilson 2008.…”

“…The mechanisms involved in the effect of CXCR7 on tumor progression were studied by Zhang et al who showed that CXCR7 regulates growth and metastasis of PTC cells via the activation of the PI3K/AKT pathway and its downstream NF-κB signaling, as well as via the downregulation of cell differentiation, by downregulating Notch signaling (Zhang et al 2015). Furthermore, Zhang et al (2016) recently reported that a high expression of CXCR7 increases both CXCL8 and VEGF levels, two main molecules with proven pro-tumorigenic effect (Rotondi et al 2018).…”

CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression

“…Moreover, doxorubicin time-and dose-dependently enhanced CCL20 expression in SKOV3 cells. The aberrant expressions of chemokines were often found in various tumors (Gao and Fish, 2018;Karin, 2018;Rotondi et al, 2018;Zhao et al, 2018). CCL20 belongs to CC chemokine family and plays key roles in the development of different kinds of cancers.…”