Altered levels of plasma chemokines in breast cancer and their association with clinical and pathological characteristics

Abstract

Chemokines are a family of small, structurally related cytokines with chemoattractant and activation properties. In breast cancer, both epithelial cancer cells and cells within the microenvironment secrete chemokines with either tumor-promoting or anti-malignant potential. The equilibrium between these two chemokine activities plays a key role in the biology of the developing tumor, including its ability to metastasize. Here we evaluated the expression of chemokines in breast tumors and the plasma of breast cancer patients before treatment in order to identify a blood-based signature that could distinguish between malignant and non-malignant processes.We screened the mRNA expression of chemokine genes using cDNA microarray on homogenous, laser-capture microdissected breast cancer specimens. Further, using a protein array approach, we determined the levels of selected chemokines in the plasma of patients with breast cancer, benign breast tumors and healthy women. Finally, we analyzed the association between the levels of chemokines in breast and blood samples with the pathological characteristics of the disease.At mRNA level, 27 chemokines and 11 chemokine receptors were differentially expressed in cancers when compared with normal breast tissue. When compared to benign tumors, the only chemokine significantly upregulated in cancers was CXCL10. At protein level, with the exception of CXCL13, nine out of the ten selected chemokines (CCL2, CCL7, CCL18, CCL22, CXCL8, CXCL9, CXCL10, CXCL11 and osteoprotegerin) were significantly overexpressed in the plasma of breast cancers patients compared to healthy controls. After grouping, CXCL8, CXCL9 and CCL22 proved to be significant predictors for breast cancers as compared to healthy controls in a model of logistic regression. We found upregulation of CXCL8, CXCL11 and CXCL9 in triple negative carcinomas, CXCL9 in low proliferative carcinomas, and CXCL10, CCL7 and osteoprotegerin in poorly differentiated carcinomas. Furthermore, CXCL9 was overexpressed in lymph node negative tumors, whereas CXCL8 and CCL18 were higher in advanced stage carcinomas.We identified a panel of chemokines dysregulated in breast cancer that could be further investigated as prospective novel diagnostic markers or for therapeutic and prognostic applications.

The effects of flaxseed and tamoxifen on the inflammatory microenvironment in normal breast tissue and in breast cancer

“…OPN correlated with fewer inflammatory mediators in breast cancer tissue than in normal breast tissue, and correlated only to CXCL9 and MMP-1,-2,-3,-12 (table 3). Several CKs are upregulated in breast cancer and specifically CCL2 and CCL5 are associated with higher tumor grade and poor prognosis (182)(183)(184). uPA is associated with poor prognosis and is validated as a prognostic biomarker in breast cancer (194,202).…”

“…In an analysis of gene-expression of CKs in breast cancer, 27 CKs were upregulated in breast cancer tissue compared to adjacent normal breast tissue and nine of these CKs also showed elevated levels in plasma compared to healthy controls (182). In breast cancer, CCL2 and CCL5 is highly expressed in both tumor and stromal cells and are associated with high tumor grade and poor prognosis (183).…”

MDC and BLC are independently associated with the significant risk of early stage lung adenocarcinoma

“…There is evidence that MDC was up-regulated in some tumor entities, suggesting its oncogenic potentials [27, 28]. The down-regulation of MDC in turn suggested its tumor suppressive potentials [29].…”

CXCL8, IL-1β and sCD200 are pro-inflammatory cytokines and their levels increase in the circulation of breast carcinoma patients

“…Overexpression of CXCL8, an angiogenic factor, by tumor cells is well known (20) and its level was correlated with breast and colon cancer progression (21)(22)(23)(24). IL-1β is another proinflammatory molecule.…”