Overexpression of <i>PCDHB9</i> promotes peritoneal metastasis and correlates with poor prognosis in patients with gastric cancer

Mukai, Shoichiro; Oue, Naohide; Oshima, Takashi; Imai, Takeharu; Sekino, Yohei; Honma, Reiko; Sakamoto, Naoya; Sentani, Kazuhiro; Kuniyasu, Hiroki; Egi, Hiroyuki; Tanabe, Kazuaki; Yoshida, Kazuhiro; Ohdan, Hideki; Yasui, Wataru

doi:10.1002/path.4931

Cited by 24 publications

(42 citation statements)

References 40 publications

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“…Several lines of evidence suggest that some integrins play an essential role in bone metastasis in PCa . Our previous study has shown that protocadherin B9 promotes peritoneal dissemination through ITGA3 , ITGA4 , ITGA5 , and ITGB1 in gastric cancer . These lines of evidence indicate that the interaction between protocadherin B9 and integrins is involved in metastasis.…”

Section: Discussionmentioning

confidence: 89%

“…We previously demonstrated that PCDHB9 modulated ITGA3, ITGA4, ITGA5, and ITGB1 through NF-κB signaling in gastric cancer. 14 We therefore investigated the effect of PCDHB9 on the expression of ITGA3, ITGA4, ITGA5, ITGB1, and transcription factor p65. The qRT-PCR showed that the overexpression of PCDHB9 induced the expression of ITGA3, ITGA4, ITGA5, and ITGB1 ( Figure S3A).…”

Section: Protocadherin B9 Induces the Expression Of Itga3 Itga4 Imentioning

confidence: 99%

“…20,30,31 Our previous study has shown that protocadherin B9 promotes peritoneal dissemination through ITGA3, ITGA4, ITGA5, and ITGB1 in gastric cancer. 14 Bicalutamide has been widely used as a first-line treatment for PCa.…”

Section: Most Patients With Advanced Pca Have Incurable Bone Metastasismentioning

confidence: 99%

“…Collectively, these findings suggest that protocadherins play an oncogenic or tumor suppressive role in PCa. We previously identified PCDHB9 , which encodes the protocadherin B9 protein and observed that the overexpression of protocadherin B9 promotes peritoneal dissemination in gastric cancer . However, there is no evidence about the role of protocadherin B9 in PCa.…”

Section: Introductionmentioning

confidence: 99%

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Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients

Sekino

Oue

Mukai³

et al. 2018

The Prostate

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Background Prostate cancer (PCa) is a common malignancy worldwide and is the second leading cause of cancer death in men. The standard therapy for advanced PCa is androgen deprivation therapy (ADT). Although ADT, including bicalutamide treatment, is initially effective, resistance to bicalutamide frequently occurs and leads to the development of castration‐resistant PCa. Thus, clarifying the mechanisms of bicalutamide resistance is urgently needed. We designed this study to assess the expression and function of PCDHB9, which encodes the protocadherin B9 protein. Methods The expression of PCDHB9 was determined using immunohistochemistry and a qRT‐PCR. The effects of the overexpression or knockdown of PCDHB9 on cell growth, migration, adhesion were evaluated. To evaluate the PCDHB9‐mediated effects in PCa, we performed a gene expression analysis using DU145 transfected with PCDHB9. We examined the effects of PCDHB9 inhibition on bicalutamide resistance. Results The qRT‐PCR revealed that the expression of PCDHB9 was much higher in PCa than that in non‐neoplastic prostate tissues. In 152 clinically localized PCa cases immunohistochemistry showed that 59% of PCa cases were positive for protocadherin B9. A Kaplan‐Meier analysis showed that the high expression of protocadherin B9 was associated with PSA recurrence after radical prostatectomy. A functional analysis showed that PCDHB9 modulated cell migration and adhesion. We also found that PCDHB9 induced the expression of ITGB6 based on a gene expression analysis. The effect of PCDHB9 inhibition on bicalutamide sensitivity was examined using MTT assays. The IC50 value of PCDHB9 siRNA‐transfected PCa cells was significantly lower than that of negative control siRNA‐transfected cells. Furthermore, immunohistochemical staining of protocadherin B9 in 74 PCa patients who were treated with androgen depletion therapy, including bicalutamide treatment, demonstrated that the high expression of protocadherin B9 was significantly associated with poor overall survival. Conclusions PCDHB9 plays an important role in the progression of PCa and bicalutamide resistance. Collectively, our results suggest that PCDHB9 targeted therapy may be more effective than bicalutamide alone.

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Section: Discussionmentioning

confidence: 89%

Section: Protocadherin B9 Induces the Expression Of Itga3 Itga4 Imentioning

confidence: 99%

Section: Most Patients With Advanced Pca Have Incurable Bone Metastasismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients

Sekino

Oue

Mukai³

et al. 2018

The Prostate

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“…Cell-cell interaction is important for cancer cell survival in arduous environments. Protocadherin β-9 may promote the formation of spheroid colonies of gastric cancer cells, and thus aid the survival of cancer cells in the ascites environment and prevent anoikis and apoptosis induced by chemotherapeutic agents (18). Additionally, intraperitoneal mesenchymal cells may support long-distance migration of disseminated tumor cells by maintaining direct contract, as observed with MKN45 gastric cancer cells (19).…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

Chen

Jin

et al. 2018

biom rep

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Abstract. The prognosis of patients with peritoneal dissemination from gastric cancer is poor, and the underlying molecular mechanism remains unclear. Exosomes, as macromolecular phospholipid bilayer vesicles comprising of proteins, nucleic acids and lipids, serve as mediators of cell-cell communication. Gastric cancer tumor-derived exosomes may be involved in the pathological process of peritoneal dissemination by mediating crosstalk between cancer cells and mesothelial cells, to result in the induction of enhanced tumor growth, migratory, adhesive and invasive abilities, peritoneal fibrosis and apoptosis, mesothelial-to-mesenchymal transition, angiogenesis and chemoresistance. The present review focuses on previous studies addressing the exosome-dependent molecular transfer in peritoneal dissemination in gastric cancer and the potential clinical applications. Contents1. Introduction 2. Exosomes in peritoneal dissemination of gastric cancer 3. Early detection by exosomal miRNAs 4. Chemoresistance and exosome-based treatment of peritoneal dissemination cases of gastric cancer IntroductionPeritoneal dissemination is detected in 14% of patients with gastric cancer at the time of initial diagnosis, for whom the median survival time is 4 months (1). Gastric cancer patients with peritoneal dissemination cannot undergo radical surgery, and the chemotherapeutic effect is limited due to inadequate distribution of intravenous chemotherapy drugs, blocked by the peritoneal barrier, and tumor chemoresistance (2). The 5-year survival rate of gastric cancer patients with peritoneal dissemination is only 2% (3). Peritoneal dissemination is among the most common patterns of recurrence in gastric cancer patients (4). However, it remains unclear how peritoneal dissemination exactly occurs, and there is a need to reveal the underlying molecular mechanism, as well as to develop more effective treatment strategies. Exosomes are macromolecular, phospholipid bilayer vesicles comprised of proteins, nucleic acids and lipids (5). At 40-120 nm in diameter, exosomes are smaller than other vesicles including microvesicles (100 nm-1 µm) and apoptotic bodies (50 nm-2 µm) (6). Exosomes exist in all body fluids and are generated by secretion and budding from various types of cells, including tumor cells (7). They contain key biological molecules including proteins, RNAs and lipids, which are considered to mediate intercellular communication (6). In particular, exosomes deliver proteins and RNAs associated with different pathologies, including neurodegenerative diseases, HIV infection, heart disease and tumor progression, from host cells to recipient cells (8). Tumor-derived exosomes (TEX) may have the capacity to remodel the tumor microenvironment to make it favorable for metastatic niches (7) and, furthermore, may alter the extracellular matrix and attract more cancer cells to the niches (9). Notably, increasing studies indicate that exosomes are involved in the peritoneal dissemination of gastric cancer. The present review focuses on how exos...

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Methylation silencing of ULK2 via epithelial–mesenchymal transition causes transformation to poorly differentiated gastric cancers

et al. 2021

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Overexpression of PCDHB9 promotes peritoneal metastasis and correlates with poor prognosis in patients with gastric cancer

Cited by 24 publications

References 40 publications

Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients

Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

Methylation silencing of ULK2 via epithelial–mesenchymal transition causes transformation to poorly differentiated gastric cancers

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