دانشگاه: University of Arkansas for Medical Sciences
: 7.95 MB
Abstract: Platelets help in maintaining vascular homeostasis via adhesion, activation, and aggregation. Some reports suggest a supportive role for platelets in the growth of primary tumors, angiogenesis, and establishment of metastatic tumors. GP Ibα is an adhesion receptor and GPVI is an adhesion and activation receptor on the platelet surface. In this dissertation, platelet GP Ibα and GPVI have been evaluated for their contributions to experimental and spontaneous metastasis in vivo. In GP1b-/- mice experimental metastasis was reduced by 95%. However, PyMT;GPIb-/- mice did not show any significant difference in spontaneous lung metastasis of breast adenocarcinoma. Experimental metastasis was also significant in the mouse colony expressing human GP Ibα. The down-stream signaling via GP Ibα was not found to be important for experimental metastasis. However a 50% reduction was found in experimental metastasis in the mouse colony expressing a variant GP Ibα with defective ligand binding properties and inside-out signaling. GPVI-/- mice showed a 50% reduction in experimental metastasis. Growth of subcutaneously induced tumors and spontaneous mammary adenocarcinoma was not diminished in GP1b-/- or PyMT;GP1b-/- mouse colonies, respectively. Together, these finding suggest that platelet receptors GP Ibα and GPVI support experimental metastasis and can be explored in depth for their therapeutic potential to treat patients with metastatic disease.