The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initia...The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.展开更多
Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requ...Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requires more representative models to be used in more innovative ways.Methods:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue.Several assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet assays.Ptychographic quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population data.Results:A combination of radiation and Vorinostat may be more effective than radiation alone.Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells.Analysis of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture.Conclusion:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity.Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.展开更多
基金We wish to acknowledge Prostate Cancer UK(RIA15-ST2-022&PhD grant S12-027)for finan cial support and sponsorship,and Yaqeen Sawalha for producing figures for this manuscript.
文摘The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.
基金funded by a PCUK Innovation Award-RIA15-ST2-022.SK was supported by a White Rose Fund studentship.
文摘Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requires more representative models to be used in more innovative ways.Methods:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue.Several assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet assays.Ptychographic quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population data.Results:A combination of radiation and Vorinostat may be more effective than radiation alone.Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells.Analysis of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture.Conclusion:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity.Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.
