Manoj Pandre, Debabani Roy Chowdhury, Sundarajan Kannan, Samrat Roy, Rajesh Kumar and Arnab Roy Chowdhury.

Tumor cell induced platelet aggregation is independent of tumor invasiveness as observed from both cell lines and primary tumors.

Platelets play a key role in the metastatic dissemination of tumor cells, by binding and protecting the invading tumor cells from shear stress and host immune system while promoting both extravasation and intravasation. Our study investigates whether the invasiveness of the tumor cell drives successful platelet aggregation and subsequent extravasation. We took four colorectal (CRC) and triple-negative breast cancer (TNBC) cell lines and confirmed that the latter was more aggressive in invasion, intravasation, and extravasation. Interestingly, for the same healthy donor (all donors were without any medication), platelet binding was not directly proportional to the invasiveness of the tumor, as CRC cells showed more aggregation than TNBC. One key difference was all the TNBC cell lines had a biphasic curve of platelet aggregation with a distinct lag time, unlike the CRC cell line SW480. Within the CRC cohort, a comparison of the non-invasive HT29 with invasive HCT116 cells, showed more platelet aggregation for HT29, albeit after a lag time. Interestingly, genetic conversion of HT29 cells to more invasive form increased platelet aggregation, whereas CRISPR CAS manipulation of invasive HCT116 further decreased platelet aggregation, for the same donor. Within the TNBC cohort, different volunteers showed different levels of aggregation for the same cell lines, with the aggregation observed for the metastatic cell line HCC1937 being less than the aggregation observed for non-metastatic MDAMB468 cells, confirming that aggregation was indeed independent of tumor invasiveness. We next assessed platelet aggregation of primary tumors, resected from treatment-naive CRC patients. Interestingly, primary cells from a lymph node-positive tumor did not show aggregation but primary cells from a lymph node-negative tumor showed aggregation, again reaffirming that tumor-induced platelet aggregation is independent of cellular invasiveness.  Our next goal is to identify the factors responsible for platelet aggregation and exploit the same for anti-metastasis drug discovery.

Poster 4_MRS_Dec 2021