Calcitonin Increases Tumorigenicity of Prostate Cancer Cells: Evidence for the Role of Protein Kinase A and Urokinase-Type Plasminogen Receptor

Thomas, Shibu; Chigurupati, Srinivasulu; Anbalagan, Muralidharan; Shah, Girish V.

doi:10.1210/me.2005-0284

Cited by 45 publications

(76 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Selection of stable transfectants was carried out with Geneticin (800 mg/ml for 3 weeks). CT-deficient PC-3M subline (PC-3M-CT K ) was generated by stable co-transfection of hammerhead ribozymes against CT mRNA and pcDNA3.1-Zeo in PC-3M cells as described recently (Thomas et al 2006). LNCaP-V cells lacked CT mRNA and did not secrete CT in the conditioned media, but LNCaP-CT cells displayed high CT mRNA abundance and secreted CT in the conditioned media.…”

Section: Cell Culturementioning

confidence: 99%

“…PC-3M-CT K cells displayed greater than 90% decrease in the abundance of endogenous CT mRNA and CT secretion when compared with their vector controls (PC-3M-V). The sublines were extensively characterized in recently published studies (Thomas et al 2006). To detect implanted tumor cells in mice, we stably transfected all PC sublines with DsRed-MCherry-Hyg-N1, a mammalian expression vector that encodes DsRed-MCherry, a derivative of red fluorescent protein (Clontech).…”

Section: Cell Culturementioning

confidence: 99%

“…Moreover, the abundance of CT/CTR mRNA correlates positively with Gleason grade of primary PCs. In addition, exogenous CT or enforced activation of CT-CTR autocrine axis causes increased tumorigenicity, invasiveness, and resistance to apoptosis in several PC cell lines (Ritchie et al 1997, Nagakawa et al 1998, Sabbisetti et al 2005b, Thomas & Shah 2005, Thomas et al 2006). However, the pathological significance of CT expression in progression of PC from localized tumor to its metastatic form has not been established.…”

Section: Introductionmentioning

confidence: 99%

“…Although cyclic AMP-dependent protein kinase plays a key role in the actions of CT, CT also activates the PI3-kinase-Akt-survivin and the b-catenin pathways , Sabbisetti et al 2005b, Thomas et al 2006).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

View full text Add to dashboard Cite

Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer (PC).Although the significance of CT-CTR axis in PC cell growth, invasion, and epithelial to mesenchymal transition has been established, its role in tumor metastasis has not been examined. To examine the role of CT-CTR axis in tumor metastasis, we employed stable CT-CTR activated and silenced system of three PC cell lines, LNCaP cells that lack endogenous CT, PC-3 cells that lack endogenous CTR, and PC-3M cells that co-express CT and CTR. Enforced expression of CT in LNCaP cells and CTR in PC-3 cells increased their ability to form orthotopic tumors and distant metastases in multiple organs. By contrast, silencing of CT expression in PC-3M cells not only reduced their tumorigenicity, but also completely abrogated their metastatic potential. To investigate the effect of in vivo silencing of CT expression on tumor growth, we employed recombinant adeno-associated virus (rAAV) to deliver anti-CT ribozymes in preexisting tumors of nude mice and large probasin promoter (LPB)-Tag transgenic mice. rAAV-CT K treatment not only abrogated the growth of pre-implanted tumors in nude mice, but also significantly reduced the growth of spontaneous tumors in LPB-Tag mice. Analysis of CT upregulated and silenced PC-3M transcriptomes revealed 105 genes affected by the modulation of CT expression. These CT signature genes generated survival, adhesion, pro-inflammatory, and pro-metastatic pathways. Added together, these data indicate a pivotal role for CT-CTR axis in PC metastasis and may serve as a potential therapeutic target for advanced PC.

show abstract

Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

View full text Add to dashboard Cite

show abstract

“…Expression of CT in tissue from the brain, prostate and uterus has been reported [3][4][5], and this suggests that it has additional functions other than those for osteoclasts and the kidney. As supporting evidence for additional functions, the CT expression levels have been shown to be related with tumorigenicity of prostate cancer [15] and to be increased in the pregnant rat uterus during implantation [4]. Furthermore, treatment with antisense olignucleotide of CT mRNA severely impairs embryo implantation [18].…”

mentioning

confidence: 96%

Expression Profile and Localization of Mouse Calcitonin (CT) Sense/Antisense Transcripts in Pre- and Postnatal Tissue Development

Rezaeian

Nishibori

Hiraiwa

et al. 2009

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Calcitonin (CT) has been shown to have various functions including osteoclast activity and calcium and phosphorus metabolism in mammals. In the present study, we measured the amounts of CT mRNA in the mouse brain, liver, kidney, heart and testis at various development stages, 14 days post-coitum (dpc), 17-dpc, newborn, 1 week and 8 weeks (adult), using real-time PCR. In the brain and kidney, the amount of CT mRNA decreased with development. In the testis, elevated amounts were observed at 17-dpc and 8 weeks. In the liver, the amount increased from the 14 dpc embryo to newborn stage and then decreased. In the heart, elevated amounts were observed at 17-dpc. Additionally, the CT antisense transcript was determined using a modified RT-PCR and nucleotide sequencing in the present study. Organs with high mRNA expressions were examined for localization of transcripts using in situ hybridization. The CT sense and antisense transcripts in the 14 dpc brain were mainly localized in the mesencephalon. In the pre-and postnatal stages, sense and antisense transcripts were shown to exist rather uniformly in the kidney, heart, liver and testis. In the 17-dpc rib and thyroid lobe and the adult ovary, the sense and antisense transcripts were found to be densely localized. KEY WORDS: calcitonin, in situ hybridization, mouse, sense/antisense transcripts.J. Vet. Med. Sci. 71 (5): [561][562][563][564][565][566][567][568] 2009 Calcitonin (CT) is a 32 amino acid peptide hormone that has been shown to participate in osteoclast activity and reabsorption of calcium and phosphorus through target organ comprised of the bone and kidney in mammals. CT is mainly produced in parafollicular cells (C cells) in the thyroid gland and is produced in a wide variety of other tissues [12]. Currently, CT is a therapeutic agent for treatment of bone diseases such as osteoporosis and Paget's disease [10,16]. Expression of CT in tissue from the brain, prostate and uterus has been reported [3][4][5], and this suggests that it has additional functions other than those for osteoclasts and the kidney. As supporting evidence for additional functions, the CT expression levels have been shown to be related with tumorigenicity of prostate cancer [15] and to be increased in the pregnant rat uterus during implantation [4]. Furthermore, treatment with antisense olignucleotide of CT mRNA severely impairs embryo implantation [18].In the past several years, the number of sense and antisense pair transcripts reported has sharply increased [7]. Due to the increase in the number of these studies, researchers have initiated investigations of not only of the localization of antisense transcripts but also of regulation of sense transcripts with their antisense transcripts in order to more fully understand the molecular interaction occurring in individual loci, cells and tissues. Changes in the expression levels of each non-coding RNA have been described for complex diseases such as cancer [1,14,17] and neurological diseases [11].However, little is known about th...

show abstract

Methods for Evaluation of Structural and Biological Properties of Antiinvasive Natural Products

Mudit

Khanfar

Shah

et al. 2011

Methods in Molecular Biology

View full text Add to dashboard Cite

Prostate cancer is considered the most common cancer form among males in Western countries. Very limited options are available for the treatment of advanced metastatic prostate cancer. More than 50% of today's anticancer drugs are natural products or derived from a natural origin. To discover new entities with potential to treat prostate cancer at androgen-refractory stages, 36 structurally diverse natural products were screened using functional-based assays. The tested compounds were selected broadly from major secondary metabolites of plants, marine invertebrates, and fungi. These diverse entities were prescreened for their antiinvasive ability against prostate cancer cells, PC-3M, using spheroid disaggregation assay. Active representatives including three selected structural classes, a macrolide, a β-carboline alkaloid, and a phenylmethylene hydantoin (PMH), were then tested for their ability to stabilize junctional complexes and enhance cell-cell adhesion of androgen independent prostate cancer cells. Transepithelial resistance (TER) and paracellular permeability assays were used to elicit the aforementioned properties. These studies led to the emergence of PMHs as a small molecule class from the marine sponge Hemimycale arabica with a unique potential to attenuate CT-stimulated prostate cancer growth, metastasis, paracellular permeability, and enhance TER and cell-cell adhesion of prostate cancer cells. The unique activities of PMHs were validated using several in vitro assays followed by in vivo testing in two mice models. A 3D QSAR was established using SYBYL 8.1-Comparative Molecular Field Analysis (CoMFA) model. This chapter includes the methodology for evaluation of structural and biological properties of new antiinvasive molecules with an exceptional potential to stabilize junctional complexes from diverse natural product sources.

show abstract

Calcitonin Increases Tumorigenicity of Prostate Cancer Cells: Evidence for the Role of Protein Kinase A and Urokinase-Type Plasminogen Receptor

Cited by 45 publications

References 46 publications

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Expression Profile and Localization of Mouse Calcitonin (CT) Sense/Antisense Transcripts in Pre- and Postnatal Tissue Development

Methods for Evaluation of Structural and Biological Properties of Antiinvasive Natural Products

Contact Info

Product

Resources

About