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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.

SUBMITTER: Zarychta E

PROVIDER: S-EPMC8072989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent studies have noted the tumor-stroma interaction as an integral part of tumor growth and spread as well as novel avenues for effective treatment. However, the details by which tumor and stroma cells communicate remain poorly understood. Here we show that the migration speed of the non-small-cell lung tumor cell line H838 is significantly increased under the influence of human pulmonary endothelial cells, HPAEC, in a transfilter co-culture system. To elucidate the effect of cell communication on the increased tumor cell migration, we record the H838 transcriptome response after the induction of migration in a hetero- and homogenous co-culture conditions. Gene Set enrichment analysis indicates a migration response of H838 in heterogenous co-culture system. Moreover, computationally transcription factor analysis relates the specific gene expression response to the cytokine-induced up-stream receptor activity and subsequently linking these factors to the upstream receptors via shortest paths across a directed protein-protein interaction network. This analysis predicted TNF- and SDF-1 signaling as well as multiple receptors upstream of Stat3 as putative mediators of the transcriptome response. To close the signaling information path from transcription factors to the possible receptor activation, we determine secretome quantification using a cytokine array. The latter revealed the predicted TNFa, SDF-1a signaling molecules as well as other known migration cytokines, like IL8 and IL6, as possible candidates for increased migration. Addition through the recombinant proteins or respected inhibitions reveal TNFa as well as SDF-1a as an immediate and early-late secreted factors that cause the increase in H838 migration. Interestingly, both factors were not regulated on the gene level of the H838 in heterogenous co-culture conditions, consequential HPAEC produce TNFa and SDF1a as shown by qPCR technique. Concluding, our combined computational and experimental approach revealed a holistic overview on the migration enhancement of lung tumor cells due to endothelial derived factors. Increase in migration is caused by an early TNFa induced inflammation response followed by a SDF-1a activity to sustaining the phenotype of migration. This tumor-endothelial-communication give a new insight for tumor migration.

Dataset Information

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

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