Abstract B18: Intratumor lysophosphatidylinositol metabolites in a treatment naive patient-derived bone metastatic prostate cancer xenograft

A patient-derived bone metastatic prostate cancer (PCa) xenograft (MDA-PCa-183) was used to investigate early resistance mechanisms after androgen deprivation therapy (ADT). The patient-derived xenograft (PDX) expresses wild-type androgen receptor (AR), TMPRSS2-ERG and was found to have homozygous loss of PTEN [1]. MDA-PCa-183 PDX was established as described by Li et al. [2] using a bone biopsy procured from a patient with metastatic PCa prior to ADT. Tumors were grown in intact male immunodeficient mice (n=23) with a subset of mice (n=16) castrated when they reached a size of approximately 900 mm3. At day 11 after castration tumors from 6 mice were harvested and these were considered at maximal androgen ablation (MAA). Of the remaining ten castrated mice, seven responded to androgen ablation by tumor shrinkage or detention of tumor growth (responsive tumors). Tumors of three mice demonstrated sustained growth after castration (relapsed tumors), were harvested between 30 to 40 days after castration and prostate specific antigen (PSA) blood levels were measured. The androgen signaling biomarkers, AR, cytochrome P450 17-alpha-hydroxylase/17,20-lyase (CYP17) and TMPSSR2-ERG protein expression were determined using immunohistochemistry. A biochemical profile consisting of lipid, amino acid, bioenergy, nucleotide (Metabolon, Inc.) and steroid were measured.The levels of testosterone, androstenedione, dihydrotestosterone, progesterone and 17-alpha-hydroxy-progestone were <0.1 p...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research