Abstract
Although treatment options in breast cancer have been improved significantly, predictive biomarkers for disease progression and metastasis are still lacking. Recent studies indicate that several TNF Receptor Superfamily members are involved in breast cancer cell proliferation and survival. Interestingly, TNFRSF13B (TACI) mRNA level were of prognostic relevance in breast cancer patients. In this study we provide evidence for TACI expression on platelets of breast cancer patients. The level of platelet-expressed TACI (pTACI) was significantly increased on platelets derived from breast cancer patients compared to healthy controls. Upon platelet activation, pTACI was downregulated on the platelet surface of healthy donors and breast cancer patients. Of note, inhibition of matrix metalloprotease (MMP) prevented downregulation of pTACI ex vivo, indicating that proteolytic cleavage of pTACI is responsible for reduction of pTACI level. Stimulation of pTACI via BAFF, BAFF 60-mer or APRIL did not influence platelet activation and function. Remarkably, pTACI was particularly regulated during tumor progression in our breast cancer cohort. TACI expression levels on platelets were correlated with clinical parameters including tumor stage, occurrence of metastasis and tumor cell proliferation (Ki67). In conclusion, our data emphasize the potential use of platelets as a liquid biomarker in breast cancer.
Highlights
Considerable data confirmed critical involvement of chronic inflammation in tumor initiation and progression [1]
While the short isoform was predominantly found in the The Cancer Genome Atlas Database (TCGA) cohort (75% of all patients), it is not known whether and how these variants are associated with tumor progression and clinical outcome in breast cancer (Supplementary Figure 1)
TACI is a receptor for APRIL, BAFF and interacts with CAML (Calcium signal-modulating cyclophilin ligand) and as such mainly known for its role in B cell immunity [26, 32]
Summary
Considerable data confirmed critical involvement of chronic inflammation in tumor initiation and progression [1]. A better understanding of the tumor-microenvironment (TME) which among others comprises a variety of immune cells is essential to further improve treatment options and the outcome of cancer patients. Besides contribution to B cell activation, proliferation and plasma cell differentiation, autocrine secretion of tumor necrosis factor (TNF) superfamily (TNFSF) members BAFF (TNFSF13B) and APRIL (TNFSF13) have been described to prevent B chronic lymphocytic leukemia (B-CLL) cells from apoptosis [9]. In breast cancer several TNF receptor superfamily (TNFRSF) members BAFF, APRIL, BCMA (TNFRSF17) and TACI (TNFRSF13B) have been associated with tumor initiation and progression [10,11,12,13]
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