Abstract 78P
Background
The critical role of platelets in cancer metastasis is widely proclaimed. While in circulation, they shield tumor cells to escape immunosurveillance and establish secondary tumors. During this interaction platelets become activated and are termed as tumor educated platelets (TEPs). Recent reports confirmed pivotal role of platelets within tumor microenvironment (TME) though, functional status of these TEPs remains elusive. This work emphasises the phenotypic and genotypic alterations in breast cancer stem cells (BCSCs) triggered by TEPs, which in turn lead to metastasis.
Methods
Frequency of humoral TEPs (CD41+/CD62P+) were analysed in murine tumor models along with luminal A (LumA) and triple-negative (TNBC) patients. Effects of TEPs (isolated from patients blood) on BCSCs were assessed by co-culturing BCSCs from MCF-7 and MDA-MB-231 with TEPs. Tumorsphere, clonogenicity, migration assays were done with validation in swiss mice to decipher the impact of TEPs on BCSCs. RT-PCR, flow cytometry, western blot, immune-staining were performed to check the status of various angiogenic and metastasis related genes.
Results
Screening of peripheral blood and breast tumor sections revealed higher frequency of TEPs in TNBC than LumA, suggesting their possible role in disease aggressiveness. Under TEPs influence BCSCs, showcased enhanced tumorigenic and clonogenic potentialities in-vitro. They exhibited migratory, invasive, angiogenic capacities with upregulated VIMENTIN, TWIST, CD31, HIF1α, MMP9 and low E-CADHERIN expression compared to non-treated BCSCs confirming their metastatic potential. This was further supported by in-vivo observation where TEP∼CSC produced numerous metastatic colonies in murine lungs. Analysis of the mechanism of action revealed that this mutual interdependency was functioning through WNT-βcatenin-VEGFR2 axis.
Conclusions
This study advocates the importance of TEPs in tumor initiation and progression. Their association with vicious BCSCs to promote metastasis acknowledges them as a novel therapeutic target.
Legal entity responsible for the study
S. Banerjee.
Funding
Council of Scientific and Industrial Research - CSIR, New Delhi, India.
Disclosure
All authors have declared no conflicts of interest.