Galectin-3 in Prostate Cancer Stem-Like Cells Is Immunosuppressive and Drives Early Metastasis

Abstract Background Prostate cancer (PCa) is a heterogeneous group of tumors, including non-aggressive (NAG) and aggressive (AG) subtypes, with variable clinical outcomes. We assessed the diagnostic utility of selected protein markers to identify AG tumors. Methods The TMA was constructed, including NAG and AG. 12 protein markers were evaluated using the TMA by IHC stains. The makers were also evaluated for their potential utility as single or panels for distinguishing AG from NAG tumors. Results The higher expressions of four protein markers, including prostate specific membrane antigen (PSMA), phospho-EGFR, androgen receptor (AR), and P16, were identified in AG tumors of Gleason score 4 and 5. In contrast, Galectin-3, DPP4 and MAN1B1 revealed stronger staining patterns in NAG tumors. Sensitivity and specificity of individual marker varied widely. In tow-marker panels, especially in the panel of DPP4 and PSMA, the specificity was 38.46% at 95% sensitivity. To further improve the detection ability, we combined DPP4 and PSMA with either Galectin-3 or phospho-EGFR into three-marker panels. The specificity achieved >46% at 95% sensitivity and AUC was >0.85. Conclusions Our panels can be used to improve the separation of AG from NAG tumor and to add in the optimization of the treatment strategy for patients.

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Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy

PLoS ONE ◽

10.1371/journal.pone.0066855 ◽

2013 ◽

Vol 8 (6) ◽

pp. e66855 ◽

Cited By ~ 334

Author(s):

Nicholas Erho ◽

Anamaria Crisan ◽

Ismael A. Vergara ◽

Anirban P. Mitra ◽

Mercedeh Ghadessi ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Early Metastasis

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Abstract 322: Functional significance of tyrosine phosphorylation of galectin-3 in prostate cancer progression

10.1158/1538-7445.am2012-322 ◽

2012 ◽

Author(s):

Vitaly Balan ◽

Pratima Nangia-Makker ◽

Avraham Raz

Keyword(s):

Prostate Cancer ◽

Tyrosine Phosphorylation ◽

Cancer Progression ◽

Functional Significance ◽

Prostate Cancer Progression ◽

Galectin 3

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Regulation of Prostate Cancer Progression by Galectin-3

American Journal Of Pathology ◽

10.2353/ajpath.2009.080816 ◽

2009 ◽

Vol 174 (4) ◽

pp. 1515-1523 ◽

Cited By ~ 70

Author(s):

Yi Wang ◽

Pratima Nangia-Makker ◽

Larry Tait ◽

Vitaly Balan ◽

Victor Hogan ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Prostate Cancer Progression ◽

Galectin 3

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Intracellular galectin-3 inhibits apoptosis in human prostate cancer

The Japanese Journal of Urology ◽

10.5980/jpnjurol.94.165_2 ◽

2003 ◽

Vol 94 (2) ◽

pp. 165

Author(s):

Tomoharu Fukumori ◽

Nangia-Makker Pratima ◽

Yukinori Takenaka ◽

Susumu Kagawa ◽

Raz Avraham

Keyword(s):

Prostate Cancer ◽

Human Prostate ◽

Human Prostate Cancer ◽

Galectin 3

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217: Expression of Galectin-3 is Associated with Resistance to Anticancer Drug-Induced Apoptosis in Prostate Cancer

The Journal of Urology ◽

10.1016/s0022-5347(18)34482-3 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 60-60

Author(s):

Tomoharu Fukumori ◽

Natsuo Oka ◽

Toshinori Kasai ◽

Tatsunori Tyubachi ◽

Masayuki Takahashi ◽

...

Keyword(s):

Prostate Cancer ◽

Anticancer Drug ◽

Drug Induced ◽

Galectin 3 ◽

Induced Apoptosis

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Combining inhibition of galectin-3 with and before a therapeutic vaccination is critical for the prostate-tumor-free outcome

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001535 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001535

Author(s):

Carolina Tiraboschi ◽

Lucas Gentilini ◽

Carla Velazquez ◽

Enrique Corapi ◽

Felipe Martín Jaworski ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Surgical Resection ◽

Immune Checkpoint ◽

Immune Escape ◽

Prostate Tumor ◽

Clinical Samples ◽

Major Health Problem ◽

Essential Questions ◽

Galectin 3

BackgroundProstate cancer (PCa) is a major health problem worldwide. Taxol derivatives-based chemotherapies or immunotherapies are usually proposed depending on the symptomatic status of the patient. In the case of immunotherapy, tumors develop robust immune escape mechanisms that abolish any protective response, and to date why prostate cancer is one of the most resistant diseases remains unresolved.MethodsBy using a combination of clinical data to study the transcriptome of metastasis samples from patients with castration-refractory prostate cancer, and state of the art cellular and molecular biology assays in samples from tumor-bearing mice that have been submitted to surgical resection of the tumor before receiving a vaccination, we answered several essential questions in the field of immunotherapy for prostate cancer. We also used two different methods to inhibit the expression of galectin-3 (Gal-3) in tumor cells: a stable RNA interference method to control the expression of this galectin efficiently only in tumor cells, and low and non-cytotoxic doses of docetaxel to easily transfer our findings to clinical settings.ResultsHerein, we show for the first time that Gal-3 expressed by prostate tumor cells is the main immune checkpoint responsible for the failure of vaccine-based immunotherapy. Our results show that low and non-cytotoxic doses of docetaxel lead to the inhibition of Gal-3 expression in PCa cells as well as in clinical samples of patients with metastatic and castration-resistant PCa promoting a Th1 response. We thus optimized a prostate cancer animal model that undergoes surgical resection of the tumor to mimic prostatectomy usually performed in patients. Importantly, using Gal-3-knocked down-PCa cells or low and non-cytotoxic doses of taxane before vaccination, we were able to highly control tumor recurrence through a direct impact on the proliferation and infiltration of CD8+ cytotoxic T.ConclusionsThus, Gal-3 expression by PCa cells is a crucial inhibitor for the success of immunotherapy, and low doses of docetaxel with non-cytotoxic effect on leukocyte survival could be used before immunotherapy for all patients with PCa to reduce the expression of this critical negative immune checkpoint, pre-conditioning the tumor-microenvironment to activate an antitumor immune response and promote tumor-free outcome.

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