Inhibition of Intercellular Communication between Prostate Cancer Cells by A Specific Anti-STEAP-1 Single Chain Antibody

Background: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is present at the intercellular junctions of the secretory epithelium of prostate and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a transporter protein or a putative channel between cancer cells while it has limited expression in normal human tissues. This protein has been suggested as an attractive target for prostate cancer immunotherapy. Objective: This study aimed at the development of a specific single chain fragment variable (scFv) antibody against STEAP-1 epitope and testing the inhibitory effect of the selected scFv antibody in blocking gap junctions between tumor cells. Method: In the current study, a phage library was used and a specific scFv antibody was isolated against STEAP-1 epitope using panning process. Results: PCR and DNA fingerprinting of the obtained clones demonstrated a dominant pattern of a specific clone. Binding of the selected scFv to the corresponding target on PC3 and LNCaP cell lines was tested using ELISA and flow cytometry techniques. The inhibitory effect of the selected scFv antibody in blocking gap junctions between the cells was tested using intercellular communication assay. The selected antibody reacted with the corresponding epitope in ELISA and bound to prostate cancer cells with an intensity of 44.6% (PC3 cells) and 73.4% (LNCap cells) as shown by FACS analysis. Intercellular communication assay indicated that dye transfer between the cells in PC3 and LNCaP cell lines treated with 1000 scFv/cell was significantly inhibited (80-90%). Conclusion: Our results suggested that the selected specific anti-STEAP1 scFv highly inhibited intercellular communication between prostate cancer cells and has the potential to be used as a new effective agent in prostate cancer immunotherapy.

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A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells

Cancer Immunology Immunotherapy ◽

10.1007/s00262-006-0131-0 ◽

2006 ◽

Vol 55 (11) ◽

pp. 1367-1373 ◽

Cited By ~ 28

Author(s):

P. Wolf ◽

D. Gierschner ◽

P. Bühler ◽

U. Wetterauer ◽

U. Elsässer-Beile

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Prostate Cancer Cells ◽

Single Chain ◽

Selective Toxicity

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Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the androgen-independent growth of prostate cancer cells

Food & Function ◽

10.1039/c7fo01983a ◽

2018 ◽

Vol 9 (4) ◽

pp. 2398-2408 ◽

Cited By ~ 6

Author(s):

Huarong Huang ◽

Yan He ◽

Lanyue Zhang ◽

Hongping Xiang ◽

Dongli Li ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Inhibitory Effect ◽

Phenethyl Isothiocyanate ◽

Prostate Cancer Cells ◽

Prostate Tumors ◽

Androgen Independence ◽

Androgen Independent

This study investigates the inhibitory effect of PEITC and DBM in combination on the progression of androgen-dependent VCaP prostate tumors to androgen independence.

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Synergistic Effect of Geranylgeranyltransferase Inhibitor, GGTI, and Docetaxel on the Growth of Prostate Cancer Cells

Prostate Cancer ◽

10.1155/2012/989214 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Bin Han ◽

Naohiro Fujimoto ◽

Mizuki Kobayashi ◽

Tetsuro Matsumoto

Keyword(s):

Prostate Cancer ◽

Synergistic Effect ◽

Cancer Treatment ◽

Cancer Cells ◽

Prostate Cancer Cell ◽

Inhibitory Effect ◽

Prostate Cancer Cells ◽

Growth Inhibitory Effect ◽

Prostate Cancer Treatment ◽

Growth Inhibitory

Most advanced prostate cancers progress to castration resistant prostate cancer (CRPC) after a few years of androgen deprivation therapy and the prognosis of patients with CRPC is poor. Although docetaxel and cabazitaxel can prolong the survival of patients with CRPC, inevitable progression appears following those treatments. It is urgently required to identify better or alternative therapeutic strategies. The purpose of this study was to confirm the anti-cancer activity of zoledronic acid (Zol) and determine whether inhibition of geranylgeranylation in the mevalonate pathway could be a molecular target of prostate cancer treatment. We examined the growth inhibitory effect of Zol in prostate cancer cells (LNCaP, PC3, DU145) and investigated a role of geranylgeranylation in the anticancer activity of Zol. We, then, evaluated the growth inhibitory effect of geranylgeranyltransferase inhibitor (GGTI), and analyzed the synergy of GGTI and docetaxel by combination index and isobolographic analysis. Zol inhibited the growth of all prostate cancer cell lines tested in a dose-dependent manner through inhibition of geranylgeranylation. GGTI also inhibited the prostate cancer cell growth and the growth inhibitory effect was augmented by a combination with docetaxel. Synergism between GGTI and docetaxel was observed across a broad range of concentrations. In conclusion, our results demonstrated that GGTI can inhibit the growth of prostate cancer cells and has synergistic effect with docetaxel, suggesting its potential role in prostate cancer treatment.

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Inhibitory effect of acetyl-11-keto-β-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2008.03.005 ◽

2008 ◽

Vol 75 (11) ◽

pp. 2112-2121 ◽

Cited By ~ 42

Author(s):

Hui-Qing Yuan ◽

Feng Kong ◽

Xiao-Ling Wang ◽

Charles Y.F. Young ◽

Xiao-Yan Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Inhibitory Effect ◽

Binding Activity ◽

Boswellic Acid ◽

Prostate Cancer Cells

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Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

PLoS ONE ◽

10.1371/journal.pone.0032846 ◽

2012 ◽

Vol 7 (4) ◽

pp. e32846 ◽

Cited By ~ 18

Author(s):

Linda Kelsey ◽

Parul Katoch ◽

Kristen E. Johnson ◽

Surinder K. Batra ◽

Parmender P. Mehta

Keyword(s):

Prostate Cancer ◽

Gap Junctions ◽

Cancer Cells ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells

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Androgen-regulated Formation and Degradation of Gap Junctions in Androgen-responsive Human Prostate Cancer Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e06-04-0280 ◽

2006 ◽

Vol 17 (12) ◽

pp. 5400-5416 ◽

Cited By ~ 30

Author(s):

Shalini Mitra ◽

Lakshmanan Annamalai ◽

Souvik Chakraborty ◽

Kristen Johnson ◽

Xiao-Hong Song ◽

...

Keyword(s):

Prostate Cancer ◽

Gap Junctions ◽

Cancer Cells ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Junctional Communication ◽

Culture Model ◽

Associated Proteins ◽

A Cell

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32—and hence the extent of gap junction formation—post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum–associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate the formation and degradation of gap junctions by rerouting the pool of Cxs, which normally would have been degraded from the early secretory compartment, to the cell surface, and enhancing assembly into gap junctions. Androgens had no significant effect on the formation and degradation of adherens and tight junction–associated proteins. The findings that in a cell culture model that mimics the progression of human prostate cancer, degradation of Cxs, as well as formation of gap junctions, are androgen-dependent strongly implicate an important role of junctional communication in the prostate morphogenesis and oncogenesis.

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miR-26a regulates extracellular vesicle secretion from prostate cancer cells via targeting SHC4, PFDN4, and CHORDC1

Science Advances ◽

10.1126/sciadv.aay3051 ◽

2020 ◽

Vol 6 (18) ◽

pp. eaay3051 ◽

Cited By ~ 4

Author(s):

Fumihiko Urabe ◽

Nobuyoshi Kosaka ◽

Yurika Sawa ◽

Yusuke Yamamoto ◽

Kagenori Ito ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

High Throughput ◽

Intercellular Communication ◽

Extracellular Vesicle ◽

Prostate Cancer Cells ◽

Biological Phenomena ◽

Vesicle Secretion

Extracellular vesicles (EVs) are involved in intercellular communication during cancer progression; thus, elucidating the mechanism of EV secretion in cancer cells will contribute to the development of an EV-targeted cancer treatment. However, the biogenesis of EVs in cancer cells is not fully understood. MicroRNAs (miRNAs) regulate a variety of biological phenomena; thus, miRNAs could regulate EV secretion. Here, we performed high-throughput miRNA-based screening to identify the regulators of EV secretion using an ExoScreen assay. By using this method, we identified miR-26a involved in EV secretion from prostate cancer (PCa) cells. In addition, we found that SHC4, PFDN4, and CHORDC1 genes regulate EV secretion in PCa cells. Furthermore, the progression of the PCa cells suppressing these genes was inhibited in an in vivo study. Together, our findings suggest that miR-26a regulates EV secretion via targeting SHC4, PFDN4, and CHORDC1 in PCa cells, resulting in the suppression of PCa progression.

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