The Role of Interleukin-8 and Its Mechanism in Patients with Breast Cancer: Its Relation with Oxidative Stress and Estrogen Receptor

Abstract

Context: Breast cancer is one of the leading causes of death among women all over the world. Prognostic markers can be used for patient survival. Likewise, these biomarkers are able to generate main information related to clinical manner of breast gland tumors. Interleukin-8 (IL-8) is a chemotactic cytokines caused initiation of an inflammatory response. Evidence Acquisition: We performed a computerized search in Medline/PubMed databases with key words: IL-8, breast cancer, and oxidative stress. Results: IL-8 secretion motivates the expression of adhesion molecule, including fibronectin in human inflammatory breast cancer cells. IL-8 activates PI3K/Akt pathway, which in turn activates NF-κB resulted up-regulation of integrin β3 expression and increases the invasion of breast cancer cells. Therefore, it seems that IL-8/PI3K/Akt/NF-κB/integrin β3 axis may be used for therapeutic intervention of breast cancer with metastasis status. NF-κB plays an important role in IL-8 gene transcription via several signals, such as LPS, TNF-alpha, and oxidative stress. Oxidative stress caused angiogenic factor production, such as vascular endothelial growth factor and IL-8 via cancer cells. Moreover, there is inverse relation between ER level and IL-8, but the mechanism of IL-8 action in estrogen receptor-negative breast cancer is largely unknown. Estrogen receptor and growth factor in breast cancer cells is influenced by mitogen activated protein kinase (MAPK) cascade, as a part of IL-8 signaling pathway. Conclusions: According to these studies, interleukin-8 may be as a main biomarker for breast cancer. It seems that signaling pathway of IL-8 may be used for therapeutic intervention of breast cancer. Also oxidative stress and breast cancer cells with lacking estrogen receptor generate more interleukin-8.

Serum Inflammation Biomarkers and Micronutrient Levels in Nigerian Breast Cancer Patients with Different Hormonal Immunohistochemistry Status

“…44,45 Angiogenesis is an important step in metastasis in which IL-8 plays a critical role. 48 Increased serum IL-8 in our breast cancer patients supports its functions in angiogenicity, neovascularization and increased propensity for metastasis as earlier studies suggested. 44,45,48 49 Thus, our data support the use of IL-8 antagonist as a plausible complementary option in the management of breast cancer patients.…”

“…48 Increased serum IL-8 in our breast cancer patients supports its functions in angiogenicity, neovascularization and increased propensity for metastasis as earlier studies suggested. 44,45,48 49 Thus, our data support the use of IL-8 antagonist as a plausible complementary option in the management of breast cancer patients. 48,49 Numerous cytokines, such as IL-6, IL-8 and TNFα have been implicated in the initiation and progression of ductal carcinoma.…”

“…44,45,48 49 Thus, our data support the use of IL-8 antagonist as a plausible complementary option in the management of breast cancer patients. 48,49 Numerous cytokines, such as IL-6, IL-8 and TNFα have been implicated in the initiation and progression of ductal carcinoma. [42][43][44][45][46][47][48][49] IL-6 is a pro-inflammatory cytokine that has multiple functions such as regulation of immune functions and hematopoiesis, inhibition of apoptosis of cancer cells and stimulation of tumor angiogenesis.…”

Glucose Transporter 4 and Interleukin 8 expression in hormone receptor negative/HER2 overexpressing breast carcinoma subtype: Correlation with biological behavior of the tumor cells and prognostic parameters

“…High IL-8 expression was found to be associated with ER-/HER2 positive breast cancers more frequently than with ER+/HER2 negative tumors by various studies and this expression was linked to histologic grading, LVI, lymph node status, and metastatic potential (Malonia et al, 2014;Lyon et al, 2008;Sheikhpour, 2017). Similarly, Bendrik and Dabrosin (2009) showed that ER-/HER2 positive breast cancer cells expressed high levels of IL-8 and were associated with higher LVI and metastatic potential than tumors with ER+/HER2-.…”

Downregulation of miR-143/145 Cluster in Breast Carcinoma Specimens: Putative Role of DNA Oncoviruses

“…Besides, IL-8 has a paracrine and/or autocrine tumor-promoting role in the manipulation of proliferation and survival of tumor cells (24). An elevated level of IL-8 motivates the expression of angiogenic growth factors and cell adhesion molecules, leading to angiogenesis and metastasis in breast cancer patients (24,25). As known, CXR-1 and CXR-2 are the leading receptors of IL-8, which are expressed in all breast cancer cells, representing the promoted sensitivity of cancer cells to IL-8 compared to normal breast cells (26).…”