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Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption.

ABSTRACT: Prostate-specific membrane antigen (PSMA), an established enzyme-biomarker for prostate cancer, has attracted considerable attention as a target for imaging and therapeutic applications. We aimed to determine the effects of PSMA-targeted photodynamic therapy (PDT) on cytoskeletal networks in prostate cancer cells. PSMA-targeted PDT resulted in rapid disruption of microtubules (alpha-/beta-tubulin), microfilaments (actin), and intermediate filaments (cytokeratin 8/18) in the cytoplasm of LNCaP cells. The collapse of cytoplasmic microtubules and the later nuclear translocation of alpha-/beta-tubulin were the most dramatic alternation. It is likely that these early changes of cytoskeletal networks are partly involved in the initiation of cell death.

SUBMITTER: Liu T

PROVIDER: S-EPMC3201799 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption.

Liu Tiancheng T Wu Lisa Y LY Berkman Clifford E CE

Cancer letters 20100508 1

Prostate-specific membrane antigen (PSMA), an established enzyme-biomarker for prostate cancer, has attracted considerable attention as a target for imaging and therapeutic applications. We aimed to determine the effects of PSMA-targeted photodynamic therapy (PDT) on cytoskeletal networks in prostate cancer cells. PSMA-targeted PDT resulted in rapid disruption of microtubules (alpha-/beta-tubulin), microfilaments (actin), and intermediate filaments (cytokeratin 8/18) in the cytoplasm of LNCaP ce ...[more]

PMID: 20452720

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Project description:BackgroundEvaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques.ObjectiveWe assessed whether positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP).Design, setting, and participantsA total of 1×106 LNCaP cells were grafted subcutaneously in the flanks of 6-8-wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm2) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after.Outcome measurements and statistical analysisLocal tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance.Results and limitationsFour weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive 68Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of 68Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01).ConclusionsIn a preclinical prostate cancer model, we show that 68Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials.Patient summaryPositron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer.

Dataset Information

Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption.

Publications

Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption.

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