Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Abstract

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

Cooperation between Angiogenesis, Vasculogenesis, Chemotaxis, and Coagulation in Breast Cancer Metastases Development: Pathophysiological Point of View

“…Chemotaxis is one of the key actions that occurs during cancer development, progression, and metastasis formation. Chemokines are signaling proteins that activate chemotaxis by controlling cell movement and stimulating proliferation [ 8 , 20 ]. They are involved in homeostasis and inflammation processes.…”

“…CXCL12 is released from cancer and cancer-adjacent stromal cells, mainly from fibroblasts [ 61 ]. It exerts its actions by binding to receptor CXCR4, which can be found on distinct types of cells, including ECs and EPCs [ 20 ]. Normal breast tissue does not express CXCR4, but it can be found on BC cells, as well as on other cancerous cells, such as kidney, lung, brain, or prostate cancers.…”

“…Metastasis formation is a highly inefficient process—only a small number of tumor cells survive in the blood circulation and manage to reach the target organs [ 17 ]. Furthermore, the colonization of a second organ by disseminated tumor cells requires a complementary and adaptable microenvironment, which supports the homing of tumor cells to distant sites with characteristic attractant molecules [ 20 ]. There are two types of metastatic niches in target organs, namely, pre-existing and induced niches.…”

“…In recent years, it has been speculated that BC cells spread systematically during the early disease stage, regardless of the primary tumor size [ 18 ]. During cancer development, numerous cell types continuously liberate signaling molecules into the microenvironment, leading to the formation of a sophisticated web of communication that attracts new cell types to remodel the tumor microenvironment [ 19 , 20 ].…”