Constitutive activation of stimulatory guanine nucleotide binding protein (GSαQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells

Chien, Jeremy; Wong, Ella Lai‐Ming; Nikes, E; Noble, Mark J.; Pantazis, Cooley G.; Shah, Girish V.

doi:10.1038/sj.onc.1202690

Cited by 38 publications

(50 citation statements)

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“…10 Intraperitoneally-administered to orthotopic PC-3M-CT+ xenografts in nu/nu nude mice, PMHs 1 and 4 significantly reduced and localized the tumor mass in the abdominal cavity and prevented the formation of distant metastases at a dose of 5 or 1 lg/g body weight/day, respectively, compared to diluent-treated mice in a 60-days in vivo study. 10,31,32 Both 1 and 4 remarkably decreased the metastasis of PC-3M-CT+ cells in most organs, and reduced size of tumor cell colonies in organs where metastases were present. 10,31,32 Three equally divided intraperitoneal doses of 2 lg of 4/g body weight/week remarkably reduced growth of primary tumors and their metastasis in reproductive organs, decreased morbidity and increased survival of LPB-Tag transgenic mice.…”

Section: Resultsmentioning

confidence: 99%

“…10,31,32 Both 1 and 4 remarkably decreased the metastasis of PC-3M-CT+ cells in most organs, and reduced size of tumor cell colonies in organs where metastases were present. 10,31,32 Three equally divided intraperitoneal doses of 2 lg of 4/g body weight/week remarkably reduced growth of primary tumors and their metastasis in reproductive organs, decreased morbidity and increased survival of LPB-Tag transgenic mice. 10 …”

Section: Resultsmentioning

confidence: 99%

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Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. a b s t r a c tThe Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl)hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)-hydantoin (4) showed potent in vitro anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT and spheroid disaggregation assays. PMHs 1 and 4 also showed significant anti-invasive activities in orthotopic xenograft and transgenic mice models. To study the effect of electronic and lipophilic parameters on the activity, a wide array of several substituted aldehydes possessing electron-withdrawing (+r), lipophilic (+p), electron-donating (Àr), and less lipophilic substituents (Àp) were used to synthesize several PMHs. Few des-phenylmethylenehydantoins and 2-thiohydanoins were also synthesized and the anti-invasive activities of all compounds were evaluated. Comparative molecular field analysis (CoMFA) was then used to study the 3D QSAR. Predictive 3D QSAR model with conventional r 2 and cross validated coefficient (q 2 ) values up to 0.910 and 0.651 were established. In conclusion, PMH is a novel antimetastatic lead class with potential to control metastatic prostate cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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“…The lower chamber received the chemoattractant medium, which consisted of 90% complete medium and 10% conditioned medium from the cultures of PC-3 M cells expressing constitutively active Gsa protein. 35 The cells also received CT and uPA antibodies as described in the Results section, which were added to the insert. The incubations were carried out for 24 hr, after which the Matrigel (along with noninvading cells) was scraped off with cotton swabs, and outer side of the insert was fixed and stained using Diff Quik staining kit (Dade Behring Diagnostics, Aguada, PR).…”

Section: Upa and Invasion Of Pc-3m Cells: In Vitro Invasion Assaymentioning

confidence: 99%

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

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Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several folds higher than that in benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation increases invasiveness of prostate cancer (PC) cells via activation of protein kinase A. Since the role of urokinase-type plasminogen activator (uPA) in invasion of PC has been established, we tested the hypothesis that CT increases invasion of PC cells by stimulating uPA secretion from PC cells. Exogenously added CT stimulated the secretion of uPA from PC-3M cells in a dose-dependent manner, which was blocked by Rp.cAMP, a competitive inhibitor of protein kinase A. CT stimulated the secretion of MMP-2 and MMP-9 from PC-3M cells, and also increased their invasiveness. Both these actions of CT were blocked by uPA-neutralizing antibodies. Immunofluorescence studies with PC-3M cells suggest that CT stimulated redistribution of cellular uPA to focal adhesion sites, which was further confirmed by co-immunoprecipitation of uPA with focal adhesion kinase (FAK) in response to CT. These results suggest that CT increases invasiveness of PC cells by stimulating PKA-mediated uPA secretion and by redirecting the secreted uPA to focal adhesion sites. The results also suggest that uPA may, at least in part, mediate proinvasive actions of CT on PC cells by stimulating the secretion of gelatinases and degradation of focal adhesion sites. ' 2005 Wiley-Liss, Inc.

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“…32 Prostate cancer cells (2.5 Â 10 5 cells per well expressing hairpin double-stranded CD44v interfering RNA or controls) were seeded in the upper insert in a serumfree basal medium (RPMI 1640 medium containing 0.1% BSA, 150 mg/ml of G418, 4 mM L-glutamine, 100 mg/ml penicillin G and 100 mg/ml streptomycin). The lower chamber contained chemoattractant medium consisting of 70% complete medium, 10% fetal bovine serum, and 20% conditioned medium obtained from subconfluent cultures.…”

Section: Invasion Studymentioning

confidence: 99%

“…If abrogation of overexpression of these cell adhesion molecules impairs cancer cell survival or metastasis, gene therapy may be targeted to them. A component of the current study was to determine whether G s a cells, PC cells which have a constitutively active G s a 31 and demonstrate increased invasiveness, 32 also overexpress CD44v9 or Muc18. Finally, we acquired a CD44v10 antibody and performed immunostaining on a prostate tissue microarray in order to determine whether CD44v10 is increased in PC at the protein level along with CD44v7-9, as we showed previously.…”

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confidence: 99%

Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18

Omara-Opyene

Qiu

Shah

et al. 2004

Laboratory Investigation

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The standard form of cell adhesion glycoprotein CD44 is a metastasis suppressor in prostate cancer. However, we previously showed by RT-PCR and Western blotting that cancer overexpresses unique CD44 variant v7-v10 isoforms. Muc18 is another cell adhesion marker reportedly overexpressed by prostate cancer. Matched frozen section-confirmed tumor and benign tissues were harvested from 10 prostatectomy specimens and tumor was microdissected from two lymph node metastases. Tissues were homogenized for RNA preparations, and RT-PCR was performed for the CD44v7-v10 sequence. In cultured prostate cancer cells, we caused RNA interference against CD44v9 and/or Muc18. We used PC3M cells and a derivative cell line called G s a, that constitutively expresses this G-protein and is more invasive. Lipofection was performed for a green fluorescent protein plasmid and for two 22-mer DNA fragments, cloned into a plasmid expression vector to generate hairpin, interfering dsRNA. Assays for invasion into Matrigel, a basement membrane matrix, were performed in 4-5 experiments. RT-PCR demonstrated expression of a 608 bp band representing CD44v7-v10 or a 638 bp band of Prostate cancer remains a public health problem of enormous magnitude; it is the second most common cause of cancer fatality among North American men and the most common in Great Britain. Only a minority of all cases invade locally and metastasize, thus requiring altered expression of cell adhesion molecules to allow tumor cell detachment, migration through a stromal matrix, and lymphovascular invasion.CD44, a family of transmembrane glycoproteins involved in homotypic cell, cell-matrix, and cellcytoskeletal interaction, holds promise as a prostate tumor marker. The extracellular domain of CD44 binds numerous matrix substituents: hyaluronic acid, heparin-affinity growth factors, vascular endothelial growth factor, p185 HER2 , epidermal growth factor, and hepatocyte growth factor. Its intracellular domain binds to ezrin, radixin, moesin and merlin, which interact with the cytoskeleton; notably, neutral endopeptidase 24.11 competes with CD44 for this interaction. 1 CD44 also binds directly to the cytoskeletal substituent ankyrin, thus determining cell and tissue architectural form. 2 CD44 is an oncodevelopmental protein, with roles in

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Constitutive activation of stimulatory guanine nucleotide binding protein (GSαQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells

Cited by 38 publications

References 35 publications

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18

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