Platelet cloaking of circulating tumour cells in patients with metastatic prostate cancer: Results from ExPeCT, a randomised controlled trial

Abstract

Background Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer. Methods Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information. Results Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393). Conclusion The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC. Trial registration ClincalTrials.gov identifier NCT02453139.

Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21)

“…In all, 61 participants were randomized to the exercise or control group and had at least an initial (T0) blood sample taken for assessment. The clinical and pathological features of the participants and their diagnostic biopsies were reported previously [ 16 ]. Eleven participants (18%) had a normal BMI (<25 kg/m 2 ).…”

“…Blood samples were acquired from each participant for ScreenCell ® filtration in 3 mL K2-EDTA tubes (Grenier Bio, Monroe NC USA) using a 23-gauge, 3/4 inch butterfly needle. Up to four tubes were acquired at each blood draw (yielding a total of up to 12 mL on each occasion) and processed with ScreenCell ® Cyto filtration units within four hours according to previously published protocols [ 16 ]. Filters were stained with May–-Grunwald–Giemsa (MGG), stored at 4 °C and examined by a pathologist (BH) using an Olympus BX41 light microscope (Olympus Corporation, Tokyo, Japan) with 10× and 40× Olympus Plan Fluorite objective lenses and a 20× Olympus Plan Apo objective lens.…”

“…As described previously [ 16 ], CTCs were defined as cells in the same plane of focus as filter pores whose nucleus was at least twice the diameter of a filter pore, dark blue/purple in colour, generally of uniform staining intensity and with an outline which was well-defined around its entire circumference. Many CTCs were centred on filtration pores and had markedly irregular nuclear contours, but these were not considered definitional features.…”

“…Regular exercise has well-documented benefits in PrCa, both for primary prevention, amelioration of treatment-related side-effects, and increasingly for improved cancer-specific overall and progression-free survival (reviewed [ 15 ]). The primary endpoints of the ExPeCT trial have been published [ 16 ]. CTC numbers varied over time, but no significant differences in CTC numbers were found between non-exercise and exercise cohorts, or between overweight participants and those of normal weight.…”

Platelets Lead Morphological, Phenotypic and Functional Changes in Tumor Cells.

“…A large body of literature related with the role of platelets in cancer has been particularly focused on their ability to facilitate circulating tumor cells (CTCs) extravasation and to protect them from shear forces and assault of natural killer (NK) [25,26]. However, most of these studies do not describe structural (lipids and protein) transference promoting tumor cell membrane modi cations and not only platelet cloaking [27].…”