Fig. 7

Hypothesized molecular coordination between Cat-K-induced platelet aggregation and crosstalk with epithelial-mesenchimal-like cells from patients with breast cancer. The activation and release of cat K occurs in epithelial-mesenchimal transition cells in breast cancer subtype Luminal B. (a) Breast cancer cells cultured with human platelets and activated by cat K and α-thrombin. Phase contrast images of epithelial-mesenchimal-like cells co-cultured with platelets activated by cat K for 24 h. (b) Cat K may activate PAR-3 and PAR-4 in human platelets, by receptor cleavage, and trigger platelet aggregation. Activated PAR-3 and PAR-4 can perpetuate the cohesion of tumor cells during heteroaggregation with increase in P-selectin and CD44. The crosstalk between platelets activated by cat K and epithelialmesenchimal tumor cells form microaggreates and promote up-regulation of Hedgehog ligands and growth factors such as SHH, OPN, PTHrP, and TGFß. (c) Mammary stroma (1), intravasation (2), cat K secretion by epithelialmesenchimal tumor cells (3), and activate human platelets that could directly affect the expression of the ligands of Hedgehog signaling, reported as an aberrantly activated pathway in breast cancer and related to bone metastasis markers