Abstract
Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period.
Highlights
Prostate cancer (PCa) is among the top three most prevalent cancers among males [1] and the second leading cause of cancer related deaths in men in the United States [2]
Death from PCa does not occur because of formation of the primary tumor, but rather the progression to metastatic disease. This highlights the primary concern for PCa patients is the successful treatment of metastatic tumors. a recent meeting held by the Prostate Cancer Foundation which addressed issues hampering the translation of bench to bedside discoveries resulting from research generated in animal models [3]
Progression of this tumor model followed the clinical course of castrate resistant prostate cancer development via initial loss of AR nuclear localization to the cytoplasm before regaining AR transactivation and phenocopying the parental androgen sensitive tumor [6]
Summary
Prostate cancer (PCa) is among the top three most prevalent cancers among males [1] and the second leading cause of cancer related deaths in men in the United States [2]. Current transgenic mouse models of PCa very rarely reflect molecular features of prostate cancer initiation and progression that correlate with human disease.
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