Plexin-B1 mutation drives prostate cancer metastasis

AbstractProstate cancer mortality is associated with the metastatic spread of tumour cells. A better understanding of the mechanisms which allow a locally advanced tumour to disseminate around the body will identify new therapeutic targets to block this process. One of set of genes implicated in metastasis are plexins, which can promote or suppress tumour progression depending on cancer type and cellular context. We have taken a mouse genetics approach to gain insight into the role of Plexin-B1 in prostate cancer progression in vivo.We show here that genetic deletion of Plexin-B1 in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mouse prostate cancer models significantly decreased metastasis. High levels of prostate epithelial cell-specific expression of wild-type Plexin-B1 in knock-in mice with a PbCre+Ptenfl/flKrasG12V background also significantly decreased metastasis. In contrast, expression of a Plexin-B1 mutant (P1597L; identified from metastatic deposits in prostate cancer patients) in prostate epithelial cells in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mice significantly increased metastasis, in particular metastasis to distant sites. In line with these findings, both deletion and overexpression of wild-type Plexin-B1 reduced invasion of tumour cells into the prostate stroma, while overexpression of mutant Plexin-B1 significantly increased invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Invasion and metastasis also correlated with phosphorylation of myosin light chain, suggesting that Plexin-B1 signals via the Rho/ROCK pathway to promote metastasis.Our results demonstrate that mutant Plexin-B1 promotes metastasis in prostate cancer and represents a new therapeutic target to suppress tumour spread.

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Pancytopenia as an initial manifestation of prostate cancer: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02843-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Marcos Antonio Custódio Neto da Silva ◽

Vitor Pimentel Rodrigues Manhães ◽

Luadir Gasparotto Júnior ◽

Daniela Miti Lemos Tsukumo ◽

Cristina Alba Lalli

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Metastasis ◽

Cancer Type ◽

Initial Manifestation ◽

Additional Information ◽

Cancer Management ◽

Urinary Tract Symptoms ◽

Prostate Cancer Metastasis ◽

Tumor Involvement

Abstract Background Prostate adenocarcinoma is the most frequent cancer type among men, followed by skin cancer. Patients with prostate cancer usually present lower urinary tract symptoms due to tumor involvement. Bone marrow invasion is associated with prostate cancer metastasis and is common if blastic lesions in bones are present but is very rare without a large bone involvement and uncommon as initial presentation. Case presentation We present a case of an 86-year-old Caucasian man with bone marrow invasion of prostate cancer without urological or bone-related symptoms and without prostate nodules. His findings were dyspnea, fatigue, and tachycardia. We detail the complete investigation of the case until we found the accurate diagnosis. The patient started treatment, but he had no response and so the oncology team started palliative care. Conclusion Bone marrow invasion as an initial manifestation of prostate cancer is not common, especially if no prostatic lesions are found. This report is important to provide additional information about prostate cancer management.

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Study of gene expression changes in primary prostate cancer of mice treated with Urtica dioica L

Yafteh Lorestan University of Medical Sciences ◽

10.32592/yafteh.2021.23.2.4 ◽

2020 ◽

pp. 35-45

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cancer Progression ◽

The Body ◽

Pten Gene ◽

Control Group ◽

Root Extract ◽

Hydroalcoholic Extract ◽

Mouse Prostate ◽

Soxhlet Apparatus

Background: The role of tumor suppressor genes in the development of prostate cancer is well known. Decrease or lack of expression of these genes causes the tumor to spread through metastasis to other tissues of the body. Since nettle has anti-cancer effects, the aim of this study was to investigate the effects of hydroalcoholic extract of nettle stem and root on the expression changes of PTEN, MAGI-2 and SMAD-2 genes in mouse prostate induced tumor. Materials and Methods: In this experimental study, hydroalcoholic extract of nettle was prepared by Soxhlet apparatus. The mice were injected subcutaneously for 28 days after injection of DMBA carcinoma with doses of 75 and 250 mg/kg, respectively. Also, the control group received no drug and the sham group received only the extract. The expression changes of the target genes were analyzed by Real Time PCR and the results were analyzed statistically. Results: The results showed that PTEN gene expression was increased in treatment with 250 root extract compared to day 14 turmeric. Expression of MAGI-2 gene was increased in treatment with root extract of 75 dose on day 28 compared to day 28 tumor. Evaluation of SMAD-2 gene expression showed that expression of this gene in treatment group with 250 root extract increased on day 21 compared to day 21 tumor. Conclusion: According to studies on PTEN, MAGI-2 and SMAD-2 have revealed that inactivation of these three genes is considered a risk for cancer progression.

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Abstract 5183: Identification and characterization of wild type kinases driving prostate cancer metastasis

10.1158/1538-7445.am2015-5183 ◽

2015 ◽

Author(s):

Claire Faltermeier ◽

Justin Drake ◽

Peter Clark ◽

Bryan Smith ◽

Colleen Mathis ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Metastasis ◽

Wild Type ◽

Prostate Cancer Metastasis ◽

Identification And Characterization

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Endocytic Adaptor Protein Epsin Is Elevated in Prostate Cancer and Required for Cancer Progression

ISRN Oncology ◽

10.1155/2013/420597 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Kandice L. Tessneer ◽

Satish Pasula ◽

Xiaofeng Cai ◽

Yunzhou Dong ◽

Xiaolei Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Mouse Model ◽

Cancer Cells ◽

Potential Role ◽

Adaptor Protein ◽

Wild Type ◽

Prostate Cancer Cells ◽

Prostate Tumorigenesis ◽

Tramp Mouse ◽

Mouse Prostate

Epsins have an important role in mediating clathrin-mediated endocytosis of ubiquitinated cell surface receptors. The potential role for epsins in tumorigenesis and cancer metastasis by regulating intracellular signaling pathways has largely not been explored. Epsins are reportedly upregulated in several types of cancer including human skin, lung, and canine mammary cancers. However, whether their expression is elevated in prostate cancer is unknown. In this study, we investigated the potential role of epsins in prostate tumorigenesis using the wild type or epsin-deficient human prostate cancer cells, LNCaP, in a human xenograft model, and the spontaneous TRAMP mouse model in wild type or epsin-deficient background. Here, we reported that the expression of epsins 1 and 2 is upregulated in both human and mouse prostate cancer cells and cancerous tissues. Consistent with upregulation of epsins in prostate tumors, we discovered that depletion of epsins impaired tumor growth in both the human LNCaP xenograft and the TRAMP mouse prostate. Furthermore, epsin depletion significantly prolonged survival in the TRAMP mouse model. In summary, our findings suggest that epsins may act as oncogenic proteins to promote prostate tumorigenesis and that depletion or inhibition of epsins may provide a novel therapeutic target for future prostate cancer therapies.

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Characterization of the effects of 3,3'-diindolylmethane (DIM) in the TRAMP mouse prostate cancer model and DIM's interaction with estrogen receptor signaling

10.32469/10355/69862 ◽

2018 ◽

Author(s):

◽

Yufei Li

Keyword(s):

Prostate Cancer ◽

Estrogen Receptor ◽

The Body ◽

Cruciferous Vegetables ◽

Protective Effects ◽

Working Mechanism ◽

Estrogen Receptor Signaling ◽

Mouse Prostate ◽

Prostate Cancer Model

3,3'- diindolylmethane (DIM) is an acid -derived compound formed during the digestion of indole-3-carbinol (I3C), which is one of the main compounds in cruciferous vegetables, such as broccoli, cabbage and kale. Studies indicate that the cancer protective effects of cruciferous vegetables and I3C partially rely on DIM, which is the bioactive form of I3C in the body, and DIM has been shown to interact with several signaling pathways in cancer. However, the primary molecular working mechanism of DIM is still not clear. In this dissertation, we hypothesize that DIM works through estrogen receptor (ER) signaling to inhibit prostate cancer. We focus on DIM's interaction with ER, as well as its effects on preventing advanced prostate cancer and weight gain in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) model.

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A rise in T3/T4 ratio reduces the growth of prostate tumors in a murine model

Journal of Endocrinology ◽

10.1530/joe-20-0310 ◽

2020 ◽

Vol 247 (3) ◽

pp. 225-238

Author(s):

Ana Sánchez-Tusie ◽

Carlos Montes de Oca ◽

Julia Rodríguez-Castelán ◽

Evangelina Delgado-González ◽

Zamira Ortiz ◽

...

Keyword(s):

Prostate Cancer ◽

Body Weight ◽

Tumor Growth ◽

Cancer Progression ◽

Cancer Cell Line ◽

The Body ◽

Prostate Tumors ◽

Mouse Prostate

Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasion of tumors. In vitro, in the LNCaP prostate cancer cell line, we found that both T3 and T4 increased the number of viable cells (Trypan blue assay), and only T4 response was fully blocked in the presence of an integrin-binding inhibitor peptide (RGD, arginine-glycine-aspartate). In summary, our data show that the prostate was highly sensitive to physiological T3 doses and suggest that in vivo, an increase in the T3/T4 ratio could be associated with the reduced weight of prostate tumors. Longitudinal studies are required to understand the role of thyroid hormones in prostate cancer progression.

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