Profiling the tumor microenvironment proteome in prostate cancer using laser capture microdissection coupled to LC⿿MS⿿A technical report

Staunton, Lisa; Tonry, Claire; Lis, Rosina T.; Finn, Stephen P.; O’Leary, John; Loda, Massimo; Bowden, Michaela

doi:10.1016/j.euprot.2015.11.001

Cited by 13 publications

(11 citation statements)

References 16 publications

(13 reference statements)

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“…Thus we consider them a satisfactory model for development of CRPC. Our group has previously applied workflows similar to those described here for proteomic profiling of the PCa tumour microenvironment using laser capture microdissected regions of patient tumour tissue [57]. Reassuringly, there is significant overlap between changing proteins identified in this cell-based study and previous tissue-based studies (data not shown), thus providing confidence that our cell line system represents a faithful model of the in vivo tumour microenvironment.…”

Section: Discussionsupporting

confidence: 52%

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

Tonry

Armstrong

2017

Oncotarget

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In the developed world, prostate cancer is the most common cancer diagnosis in men. Although prostate cancer initially presents as a non life-threatening disease, 90% of patients will develop castration resistant prostate cancer (CRPC), which preludes distant metastasis and is largely accountable for prostate cancer associated deaths. This is because as yet, there are no viable molecular therapeutic targets for effective treatment of CRPC. It is now widely accepted that cancer cells can alter their metabolic profile during the course of tumourgenesis and metastasis such that they are able to survive in oxygen and nutrient-poor environments. This work was aimed towards gaining greater mechanistic understanding of how such stresses in the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under nutrient deficient (low glucose) conditions. This led to the identification of approximately 4,000 proteins - one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of low glucose conditions was established. Novel, intuitive workflows were subsequently implemented to ensure the verification of selected proteins of interest in a robust, reproducible and high throughput manner. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC.

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Section: Discussionsupporting

confidence: 52%

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

Tonry

Armstrong

2017

Oncotarget

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“…We do, however recognize that accurately epotimizing the in vivo tumour microenvironment in a 2D cell culture system is effectively impossible. The Previously, we have applied workflows similar to those described here for proteomic profiling of the PCa tumour microenvironment using laser capture microdissected regions of patient tumour tissue [ 66 ]. Reassuringly, there is significant overlap between changing proteins identified in this cell-based study and previous tissue-based studies (data not shown), thus providing confidence that our cell line system represents a faithful model of the in vivo tumour microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression

Tonry

Armstrong

2017

Oncotarget

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Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment. This work was carried out as a continuation of a study aimed towards gaining greater mechanistic understanding of how conditions within the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under hypoxic conditions. This led to the identification of over 4,000 proteins – one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of hypoxic conditions was established. Novel, intuitive workflows were subsequently implemented to enable robust, reproducible and high throughput verification of selected proteins of interest. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC.

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“…This technique holds an immense potential given the multitude of downstream analyses that can follow (genotypic/transcriptomic profiling, signaling pathways discoveries, biomarker identification, and others; Espina et al, 2006 ). When it comes to PCa, LCM has been employed in a multitude of studies and several protocols have been established to generate downstream analyses ( Lugli et al, 2015 ; Staunton et al, 2016 ). For instance, using LCM on N-cadherin positive patient-derived subpopulations of cells, Kolijn et al (2018) demonstrated that during EMT, indoleamine 2,3-dioxygenase is overexpressed.…”

Section: Laser-capture Microdissection and Single-cell Rna-sequencingmentioning

confidence: 99%

Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development

et al. 2021

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Prostate cancer (PCa) is by far the most commonly diagnosed cancer in men worldwide. Despite sensitivity to androgen deprivation, patients with advanced disease eventually develop resistance to therapy and may die of metastatic castration-resistant prostate cancer (mCRPC). A key challenge in the management of PCa is the clinical heterogeneity that is hard to predict using existing biomarkers. Defining molecular biomarkers for PCa that can reliably aid in diagnosis and distinguishing patients who require aggressive therapy from those who should avoid overtreatment is a significant unmet need. Mechanisms underlying the development of PCa are not confined to cancer epithelial cells, but also involve the tumor microenvironment. The crosstalk between epithelial cells and stroma in PCa has been shown to play an integral role in disease progression and metastasis. A number of key markers of reactive stroma has been identified including stem/progenitor cell markers, stromal-derived mediators of inflammation, regulators of angiogenesis, connective tissue growth factors, wingless homologs (Wnts), and integrins. Here, we provide a synopsis of the stromal-epithelial crosstalk in PCa focusing on the relevant molecular biomarkers pertaining to the tumor microenvironment and their role in diagnosis, prognosis, and therapy development.

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Profiling the tumor microenvironment proteome in prostate cancer using laser capture microdissection coupled to LC⿿MS⿿A technical report

Abstract: Graphical abstract

Cited by 13 publications

References 16 publications

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression

Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development

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