Targeting Thromboxane A2 Receptor for Antimetastasis Therapy of Breast Cancer.

摘要

Dissemination and metastasis of tumor cells are major causes of morbidity and mortality in breast cancer patients. Therefore it is of vital importance to identify druggable targets to inhibit breast tumor invasion and metastasis. A critical component in the invasive growth, dissemination, and metastasis of cancer is acquisition of motility by tumor cells. Our preliminary studies suggest a novel role for the thromboxane A2 receptor (TP) in controlling breast tumor cell motility via regulating cytoskeleton reorganization. The objective of this proposal is to define the function of TP in tumor cell motility and to validate TP as a target for anti-metastasis therapy of breast cancer. In the first aim, the role of TP in breast tumor cell motility will be determined in the presence or absence of TP activation or inhibition. The isoform(s) of TP involved in tumor cell contraction and motility will be identified in the second specific aim. In the third aim, an orthotopic mouse model will be used to assess whether TP can be targeted to reduce breast cancer metastasis. The proposed studies will be highly significant toward the goals of developing mechanism-based interventions for cancers.