Role of STAMP1 on chronic stress and ADRB2 mediated tumor growth and metastasis in vivo
Aim of study: The aim of this project is to evaluation the therapeutic potentials of targeting STAMP1-ADRB2 interaction for treatment of prostate cancer in preclinical models.
Background: Six-transmembrane protein 1 (STAMP1) is overexpressed in prostatic tumors where it induces proliferation and survival of prostate cancer (PCa) cells. The molecular mechanism underlying STAMP1 function in PCa remains unclear. We have gathered in vitro evidence showing that STAMP1 favors metastasis, and would now like to confirm this finding in vivo. The results of our in vitro experiments suggest that STAMP1 negatively regulates beta2 adrenergic receptor (ADRB2) signaling, which has also been implicated in PCa. Therefore using xenograft models of PCa in which the function of ADRB2 signaling has been studied in vivo by others, we would like to test the effect of STAMP1 expression manipulation on the ADRB2-dependent effect on tumor growth and metastasis.
Methods: According to our hypothesis, we expect that manipulation of STAMP1 expression in combination with activating or inhibiting ADRB2 activity will influence the PCa tumor growth and metastasis in the animal models with engrafted PCa cells. Tumor growth and metastasis will be measured using caliper and in vivo bioluminescence.
Scientific/societal significance: The results of this project will provide us with important clues on how PCa progresses and whether STAMP1-ADRB2 signaling interact in vivo. The outcome of this project could potentially lead to novel therapeutic strategies, which would improve the survival of prostate cancer patients.
Use of animals and application of 3R: This project will use 202 nude mice. The number and use of the animals are planed and designed strictly following the guidelines of 3R principles to minimize the use of animals. The experimental procedures may cause medium distress to the animals. To enhance the animal welfare and minimize the severity, enrichments in cages, clinical/severity score sheet and necessary anesthesia will be applied.
Other: An application for extension was submitted 17/02/2021.
Background: Six-transmembrane protein 1 (STAMP1) is overexpressed in prostatic tumors where it induces proliferation and survival of prostate cancer (PCa) cells. The molecular mechanism underlying STAMP1 function in PCa remains unclear. We have gathered in vitro evidence showing that STAMP1 favors metastasis, and would now like to confirm this finding in vivo. The results of our in vitro experiments suggest that STAMP1 negatively regulates beta2 adrenergic receptor (ADRB2) signaling, which has also been implicated in PCa. Therefore using xenograft models of PCa in which the function of ADRB2 signaling has been studied in vivo by others, we would like to test the effect of STAMP1 expression manipulation on the ADRB2-dependent effect on tumor growth and metastasis.
Methods: According to our hypothesis, we expect that manipulation of STAMP1 expression in combination with activating or inhibiting ADRB2 activity will influence the PCa tumor growth and metastasis in the animal models with engrafted PCa cells. Tumor growth and metastasis will be measured using caliper and in vivo bioluminescence.
Scientific/societal significance: The results of this project will provide us with important clues on how PCa progresses and whether STAMP1-ADRB2 signaling interact in vivo. The outcome of this project could potentially lead to novel therapeutic strategies, which would improve the survival of prostate cancer patients.
Use of animals and application of 3R: This project will use 202 nude mice. The number and use of the animals are planed and designed strictly following the guidelines of 3R principles to minimize the use of animals. The experimental procedures may cause medium distress to the animals. To enhance the animal welfare and minimize the severity, enrichments in cages, clinical/severity score sheet and necessary anesthesia will be applied.
Other: An application for extension was submitted 17/02/2021.