Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study |
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Authors: | E Gazi J Dwyer N P Lockyer P Gardner J H Shanks J Roulson C A Hart N W Clarke M D Brown |
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Institution: | (1) School of Chemical Engineering and Analytical Science, The University of Manchester, P.O. Box 88, Manchester, M60 1QD, UK;(2) Histopathology Department, Christie Hospital NHS Trust, Manchester, M20 4BX, UK;(3) ProMPT Genito Urinary Cancer Research Group, The Paterson Institute for Cancer Research, The University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK;(4) Department of Urology, Hope Hospital NHS Trust, Manchester, M6 8HD, UK;(5) ProMPT Genito-Urinary Cancer Research, Cancer Research UK Paterson Institute, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK |
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Abstract: | Prostate cancer (CaP) cells preferentially metastasise to the bone marrow, a microenvironment that plays a substantial role
in the sustenance and progression of the CaP tumour. Here we use a combination of FTIR microspectroscopy and histological
stains to increase molecular specificity and probe the biochemistry of metastatic CaP cells in bone marrow tissue derived
from a limited source of paraffin-embedded biopsies of different patients. This provides distinction between the following
dominant metabolic processes driving the proliferation of the metastatic cells in each of these biopsies: glycerophospholipid
synthesis from triacylglyceride, available from surrounding adipocytes, in specimen 1, through significantly high (p ≤ 0.05) carbohydrate (8.23 ± 1.44 cm−1), phosphate (6.13 ± 1.5 cm−1) and lipid hydrocarbon (24.14 ± 5.9 cm−1) signals compared with the organ-confined CaP control (OC CaP), together with vacuolation of cell cytoplasm; glycolipid synthesis
in specimen 2, through significantly high (p ≤ 0.05) carbohydrate (5.51 ± 0.04 cm−1) and high lipid hydrocarbon (17.91 ± 2.3 cm−1) compared with OC CaP, together with positive diastase-digested periodic acid Schiff staining in the majority of metastatic
CaP cells; glycolysis in specimen 3, though significantly high (p ≤ 0.05) carbohydrate (8.86 ± 1.78 cm−1) and significantly lower (p ≤ 0.05) lipid hydrocarbon (11.67 ± 0.4 cm−1) than OC CaP, together with negative diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells.
Detailed understanding of the biochemistry underpinning the proliferation of tumour cells at metastatic sites may help towards
refining chemotherapeutic treatment. |
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Keywords: | Prostate cancer Infrared microspectroscopy Metastases Lipid |
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