Measurement of the Drug Sensitivity of Single Prostate Cancer Cells

SIMPLE SUMMARY: Cells communicate mainly through the secretion of proteins. Impaired protein secretion can indicate the development of disease. Cancer cell heterogeneity and acquired resistance to therapy are, however, reducing the effectiveness of cancer treatments. As cancer cells change during the course of the disease, sampling of cancer cells at the time of treatment is needed in order to determine which drugs will be effective. This paper describes a method for measuring secreted prostate specific antigen (PSA) protein from thousands of prostate cancer (PCa) cells. Furthermore, we show that the PSA secretion of individual cells in microwells can be stimulated or inhibited with drugs. To this end, we believe that this method could accelerate the development of new drugs, improve our understanding of resistance to therapy, and, ultimately, improve personalized cancer therapy. ABSTRACT: The treatment of cancer faces a serious challenge as cancer cells within patients are heterogeneous and frequently resistant to therapeutic drugs. Here, we introduce a technology enabling the assessment of single cancer cells exposed to different drugs. PCa cells were individually sorted in self-seeding microwells, cultured for 24 h, and then exposed to several drugs to induce (R1881) or inhibit (Enzalutamide/Abiraterone) the secretion of a protein (PSA). Cell viability and PSA secretion of each individual prostate cell were monitored over a 3-day period. The PSA protein secreted by each cell was captured on a PVDF membrane through a pore in the bottom of each well. The basal PSA secretion was found to be 6.1 ± 4.5 and 3.7 ± 1.9 pg/cell/day for LNCaP and VCaP, respectively. After exposure to R1881, the PSA secretion increased by ~90% on average and was not altered for ~10% of the cells. PSA production decreased in the majority of cells after exposure to enzalutamide and abiraterone.