Investigating the effects of androgen deprivation on the dedifferentiation of prostate cancer cells under hypoxic conditions
Poster #: 124
Session/Time: A
Author:
Arooba Ayaz, BS
Mentor:
Harold Riethman, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
Androgen deprivation therapy (ADT) is used to treat prostate cancer (PCa) in patients by decreasing the levels of circulating androgens needed by the cancer cells to grow. At first most patients are responsive to ADT; however long-term treatment is met with resistance & the development of Neuroendocrine (NE) PCa which is a rarer but more aggressive type of PCa. In vitro, PCa cells under long-term androgen deprivation become NE-like and adopt stem-like characteristics. Hypoxic conditions in the PCa microenvironment influence resistance to ADT and play a role in tumor growth and evolution by escalating the aggressiveness of tumor cells. In vivo, PCa tumors often have disorganized microvasculature leading to regions with lower oxygen concentrations within the tumor. Further research is needed to better understand the effects of ADT on PCa under hypoxic conditions.
METHODS:
Doubling time and morphological changes were assessed in PCa cells cultured under hypoxia and androgen deprivation for 8 weeks. Stage specific genes were chosen based on analysis of patient PCa tumor gene expression data from the PCa atlas. The expression of stage specific genes related to NE and stem-like dedifferentiation were determined using qPCR. CD44 Immunofluorescence was used to measure levels of CD44 expression along the 8 weeks.
RESULTS:
CD44 levels in LNCaP cells increased upon 60 days of androgen deprivation under both hypoxic and normoxic conditions but showed a larger increase under hypoxia. Morphological changes and fold change results indicate that hypoxic conditions influence the expression of NE & stem-like markers in PCa cells.
CONCLUSION:
PCa cells cultured under androgen deprivation in normoxic conditions for 8 weeks showed morphological changes and gene expression changes consistent with a NE phenotype, however the pattern in expression of NE and stem-like markers is different under hypoxia. CD44 levels along the 8 weeks increased in response to androgen deprivation as well as hypoxia with the cells cultured under both hypoxia and androgen deprivation showing the largest increase. On going experiments are in progress to further investigate how PCa cells respond to androgen inhibition under normoxic and hypoxic conditions.
Androgen deprivation therapy (ADT) is used to treat prostate cancer (PCa) in patients by decreasing the levels of circulating androgens needed by the cancer cells to grow. At first most patients are responsive to ADT; however long-term treatment is met with resistance & the development of Neuroendocrine (NE) PCa which is a rarer but more aggressive type of PCa. In vitro, PCa cells under long-term androgen deprivation become NE-like and adopt stem-like characteristics. Hypoxic conditions in the PCa microenvironment influence resistance to ADT and play a role in tumor growth and evolution by escalating the aggressiveness of tumor cells. In vivo, PCa tumors often have disorganized microvasculature leading to regions with lower oxygen concentrations within the tumor. Further research is needed to better understand the effects of ADT on PCa under hypoxic conditions.
METHODS:
Doubling time and morphological changes were assessed in PCa cells cultured under hypoxia and androgen deprivation for 8 weeks. Stage specific genes were chosen based on analysis of patient PCa tumor gene expression data from the PCa atlas. The expression of stage specific genes related to NE and stem-like dedifferentiation were determined using qPCR. CD44 Immunofluorescence was used to measure levels of CD44 expression along the 8 weeks.
RESULTS:
CD44 levels in LNCaP cells increased upon 60 days of androgen deprivation under both hypoxic and normoxic conditions but showed a larger increase under hypoxia. Morphological changes and fold change results indicate that hypoxic conditions influence the expression of NE & stem-like markers in PCa cells.
CONCLUSION:
PCa cells cultured under androgen deprivation in normoxic conditions for 8 weeks showed morphological changes and gene expression changes consistent with a NE phenotype, however the pattern in expression of NE and stem-like markers is different under hypoxia. CD44 levels along the 8 weeks increased in response to androgen deprivation as well as hypoxia with the cells cultured under both hypoxia and androgen deprivation showing the largest increase. On going experiments are in progress to further investigate how PCa cells respond to androgen inhibition under normoxic and hypoxic conditions.