Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones

Abstract

Introduction The chemokines Stromal CellDerived Factor-1a (SDF-1a/CXCL12) and Monocyte Chemotactic Protein-1 (MCP-1/CCL2) have been implicated in breast cancer progression. We recently reported elevated systemic MCP-1 in breast cancer patients. This study investigated circulating levels of SDF-1a in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines. Methods SDF-1a levels were determined by ELISA in 114 breast cancer patients and 85 controls, and correlated with clinical data. Blood samples were collected from 36 healthy premenopausal volunteers weekly for four weeks to measure Luteinising Hormone (LH), Follicular Stimulating Hormone (FSH), Oestradiol and Progesterone using a Bayer ADVIA Ò Centaur Immunoassay system, in parallel with SDF-1a and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery. Results Plasma SDF-1a was significantly higher in breast cancer patients than age-matched controls and had a significant correlation with tumour grade and epithelial subtype. Investigation of menstrual variations of these chemokines revealed lower SDF-1a levels in the mid-luteal phase of the menstrual cycle and a significant positive correlation with circulating Oestradiol. MCP-1 levels showed no correlation with menstrual hormones. There was a trend towards increased CXCL12 expression in tumour compared to normal stromal cells. Conclusions The elevated level of SDF-1a detected in breast cancer patients, and it's correlation with prognostic indicators, highlights the importance of this chemokine in disease progression. Elucidation of factors influencing chemokine secretion supports clarification of their role in tumourigenesis.Keywords Breast cancer Á Menstrual hormones Á Monocyte Chemotactic Protein-1 (MCP-1/CCL2) Á Prognosis Á Stromal Cell-derived Factor 1-a (SDF-1a/CXCL12)

Inflammatory mediators: Parallels between cancer biology and stem cell therapy

“…22 Expression of SDF-1α in breast cancer cells assists in cellular and vascular proliferation. 21 These fi ndings are consistent with studies demonstrating that plasma levels of SDF-1α are higher in patients with breast cancer than healthy individuals. 22 On the contrary, this chemokine/receptor pair appears to promote quiescence of malignant breast cells in the marrow cavity.…”

“…20 They alter the functions of target cells by paracrine, endocrine, and autocrine stimulation. 21 Chemokine receptors, such as CXCR4, in malignant cells have been shown to promote cell proliferation, migration, and maintenance. Such events contribute to metastasis, such as the role of one chemokine family, stromal cell-derived factor-1α (SDF-1α) in breast cancer invasion and metastasis to bone marrow.…”

“…Such events contribute to metastasis, such as the role of one chemokine family, stromal cell-derived factor-1α (SDF-1α) in breast cancer invasion and metastasis to bone marrow. 21,22 SDF-1α and its receptor CXCR4 are crucial to migration of breast cancer cells to sites of distant metastasis, such as bone marrow, lung, liver, and brain. 22 Expression of SDF-1α in breast cancer cells assists in cellular and vascular proliferation.…”

“…23 MCP-1 also recruits immune cells, such as macrophages, to sites of infl ammation. 21 The link to cancer is evident in studies demonstrating high levels of MCP-1 secretion by tumor cells. In patients with acute lymphoblastic leukemia, for example, MCP-1 levels are signifi cantly elevated during treatment, suggesting a regulatory mechanism in this cancer.…”

“…Interestingly, evidence suggests that the expression of the chemokines SDF-1α and MCP-1 can be regulated by endogenous hormones. 21 The prospect of regulation by endogenous hormones suggests a role for supplemental hormones as well. Therefore, the hormonal suppression of these metastasis-promoting chemokines may be one potential breast cancer treatment method.…”