Prostate Cancer Cells In Blood Research Articles

Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters.

Purpose: Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information.Experimental Design: We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA) to concurrently identify and characterize prostate cancer cells in patients' blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression.Results: The incidence of tumor cells in BMAs increased as the disease advanced: 0% in biochemically recurrent (n = 52), 26% in newly diagnosed metastatic hormone-naïve (n = 26), and 39% in metastatic castration-resistant prostate cancer (mCRPC; n = 63) patients, and their number was often higher than in paired blood. Tumor cell detection in metastatic patients' BMAs was concordant but 45% more sensitive than using traditional histopathologic interpretation of core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in BMAs than in blood, expressed higher levels of the androgen receptor protein per tumor cell, and were prognostic in mCRPC. Moreover, the patterns of genomic copy number variation in single tumor cells in paired blood and BMAs showed significant inter- and intrapatient heterogeneity.Conclusions: Paired analysis of single prostate cancer cells in blood and bone shows promise for clinical application and provides complementary information. The high prevalence and prognostic significance of tumor cell clusters, particularly in BMAs, suggest that these structures are key mediators of prostate cancer's metastatic progression. Clin Cancer Res; 23(7); 1722-32. ©2016 AACR.

Prostate Cancer: All Aspects

Prostate Cancer: All Aspects

Microfluidic, Label-Free Enrichment of Prostate Cancer Cells in Blood Based on Acoustophoresis

Circulating tumor cells (CTC) are shed in peripheral blood at advanced metastatic stages of solid cancers. Surface-marker-based detection of CTC predicts recurrence and survival in colorectal, breast, and prostate cancer. However, scarcity and variation in size, morphology, expression profile, and antigen exposure impairs reliable detection and characterization of CTC. We have developed a noncontact, label-free microfluidic acoustophoresis method to separate prostate cancer cells from white blood cells (WBC) through forces generated by ultrasonic resonances in microfluidic channels. Implementation of cell prealignment in a temperature-stabilized (±0.5 °C) acoustophoresis microchannel dramatically enhanced the discriminatory capacity and enabled the separation of 5 μm microspheres from 7 μm microspheres with 99% purity. Next, we determined the feasibility of employing label-free microfluidic acoustophoresis to discriminate and divert tumor cells from WBCs using erythrocyte-lysed blood from healthy volunteers spiked with tumor cells from three prostate cancer cell-lines (DU145, PC3, LNCaP). For cells fixed with paraformaldehyde, cancer cell recovery ranged from 93.6% to 97.9% with purity ranging from 97.4% to 98.4%. There was no detectable loss of cell viability or cell proliferation subsequent to the exposure of viable tumor cells to acoustophoresis. For nonfixed, viable cells, tumor cell recovery ranged from 72.5% to 93.9% with purity ranging from 79.6% to 99.7%. These data contribute proof-in-principle that label-free microfluidic acoustophoresis can be used to enrich both viable and fixed cancer cells from WBCs with very high recovery and purity.

Reverse transcriptase- polymerase chain reaction (RT-PCR) to detect prostate cancer micrometastasis in the blood.

Since the high mortality rate of prostate cancer is directly associated with the incidence of cancer metastasis, early detection of metastasizing prostate cancer cells in the blood has very important clinical implications. Conventional screening and staging modalities often fail to identify patients who may have prostate cancer that is already metastatic [1], and it has been estimated that 60% of new patients may have asymptomatic micrometastasis. It is therefore of great importance to be able to define which patients are at risk for the development of further metastatic disease [2,3]. It has been suggested that the detection of circulating prostate cancer cells in the peripheral blood may allow assessment of disease state [4], although the exact clinical significance of circulating cancer cells remains unclear. Animal experiments using solid tumors have shown that only two cells per milliliter of blood may be enough for tumor metastasis from hematogenous dissemination [5–7]. Based on these studies, a technique to detect circulating cells must be highly sensitive, detecting ten tumor cells in a five milliliter blood sample. Although immunohistochemical and other immunological techniques that use antibodies against tumor-associated antigens or tissue-specific antigens are helpful in detecting the primary site of metastatic disease and the presence of small foci of metastatic disease, these techniques are not sensitive enough to detect such a small number of cancer cells in a large quantity of nonneoplastic cells. It is through the development of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and new tumor markers that the desired sensitivity for this approach becomes possible. The high sensitivity and specificity obtained from this technique as well as the small quantity of test material required makes RT-PCR a definite front runner in the race for early detection of micrometastasis in prostate cancer.