Isolation and characterization of calcium sensing receptor null cells: A highly malignant and drug resistant phenotype of colon cancer

Singh, Navneet; Chakrabarty, Subhas

doi:10.1002/ijc.27902

Cited by 29 publications

(55 citation statements)

References 48 publications

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“…We hypothesize that a dynamic process of cell death and revival occurs in a culture and that CaSR null cells divide asymmetrically to replenish themselves and also differentiate into CaSR positive cells which will eventually apoptose and die. The expression profile of stem cell markers and survival markers in CaSR null cells lend support to this hypothesis.…”

Section: Discussionmentioning

confidence: 66%

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Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype

et al. 2013

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The calcium sensing receptor (CaSR) is a robust promoter of differentiation in colonic epithelial cells and functions as a tumor suppressor. Cancer cells that do not express CaSR (termed CaSR null) are highly malignant while acquisition of CaSR expression in these cells circumvents the malignant phenotype. We hypothesize that chemopreventive agents mediate their action through the induction of CaSR. Here, we compare the effectiveness of Ca(2+), vitamin D, and Aquamin (a marine algae product containing Ca(2+), magnesium and detectable levels of 72 additional minerals) on the induction of CaSR in the CBS and HCT116 human colon carcinoma cell lines and the corresponding CaSR null cells isolated from these lines. All three agonists induced CaSR mRNA and protein expression and inhibited cellular proliferation in the parental and CaSR null cells. Aquamin was found to be most potent in this regard. Induction of CaSR expression by these agonists resulted in demethylation of the CaSR gene promoter with a concurrent increase in CaSR promoter reporter activity. However, demethylation per se did not induce CaSR transcription. Induction of CaSR expression resulted in a down-regulated expression of tumor inducers and up-regulated expression of tumor suppressors. Again, Aquamin was found to be most potent in these biologic effects. This study provides a rationale for the use of a multi-mineral approach in the chemoprevention of colon cancer and suggests that induction of CaSR may be a measure of the effectiveness of chemopreventive agents.

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Section: Discussionmentioning

confidence: 66%

“…β‐actin was used as loading controls. As shown, untreated CaSR null cells do not express CaSR . The level of protein expression in cells treated with vitamin D or Aquamin was compared to that of the Ca 2+ treated cells with an assigned value of 1.0…”

Section: Resultsmentioning

confidence: 99%

Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype

et al. 2013

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“…Using miRNA array and real-time PCR, Wang et al20 found that the expression level of miR-135b was significantly upregulated in colonic cancer tissues compared with paracancerous tissues. Singh et al21 reported that the overexpression of miR-135b was associated with the reduction of tumor suppressive E-cadherin expression in colon carcinoma cell lines. Munding et al22 identified miR-135b as one of the new miRNA biomarkers for pancreatic ductal adenocarcinoma in human pancreas acinar and ductal cells by using miRNA array and real-time PCR, which has improved early diagnosis modalities and treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

Association between the expression of four upregulated miRNAs and extrathyroidal invasion in papillary thyroid carcinoma

Wang

Zhang²,

He³

et al. 2013

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BackgroundMicroRNAs (miRNAs) are important diagnostic and prognostic markers in cancer. In the study reported here, we analyzed the potential relationship between miRNA expression and extrathyroidal invasion in papillary thyroid carcinoma (PTC).MethodsSamples from 91 patients with PTC were collected from January 2008 to April 2012 at our hospital. To detect the levels of miRNA expression in fresh frozen tissues from patients with extrathyroidal invasion (n = 3) and non-extrathyroidal invasion (n = 3), miRNA array was carried out. The upregulated miRNAs between the two groups were confirmed by using real-time reverse transcriptase polymerase chain reaction.ResultsThe levels of miR-146b, miR-221, miR-222, and miR-135b were significantly higher in the extrathyroidal invasion group than in the non-extrathyroidal invasion group (P = 0.001, 0.019, 0.004, and 0.006, respectively). In addition, the miR-146b expression level was significantly higher in the massive extrathyroidal invasion group than in the minimal extrathyroidal invasion group (P = 0.016). The expression levels of miR-146b, miR-222, and miR-135b were significantly associated with tumor size (P = 0.018, 0.008, and 0.024, respectively). The upregulation of miR-146b and miR-222 was significantly associated with higher tumor-node-metastasis stage (P = 0.004 and 0.0001, respectively). The expression level of miR-222 was also correlated with age and sex (P = 0.048 and 0.002, respectively).ConclusionOur results reveal that the expression of four miRNAs correlated with extrathyroidal invasion and other clinicopathologic features in PTCs, which may support their potential clinical value as prognostic biomarkers for PTCs.

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“…Here we have shown that knockdown of km23-1 inhibited the cell migration and invasion of human CRC cells, implicating km23-1 in the motility of invasive human CRC cells. The CRC cell models employed in our studies have KRAS (or BRAF) mutations [24], [45] and/or activated epidermal growth factor receptor (EGFR) pathways [58] , but they express comparatively low levels of EMT markers (ie, Snail1/2, Twist, and FOXC2 [59]), and their morphological features are indicative of an epithelial nature [59]. Along these lines, while colon cancer is generally considered to be a molecularly heterogeneous disease, two primary intrinsic subtypes that predict disease progression and recurrence have been identified [29].…”

Section: Discussionmentioning

confidence: 99%

Decreased Tumor Progression and Invasion by a Novel Anti-Cell Motility Target for Human Colorectal Carcinoma Cells

et al. 2013

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We have previously described a novel modulator of the actin cytoskeleton that also regulates Ras and mitogen-activated protein kinase activities in TGFβ-sensitive epithelial cells. Here we examined the functional role of this signaling regulatory protein (km23-1) in mediating the migration, invasion, and tumor growth of human colorectal carcinoma (CRC) cells. We show that small interfering RNA (siRNA) depletion of km23-1 in human CRC cells inhibited constitutive extracellular signal-regulated kinase (ERK) activation, as well as pro-invasive ERK effector functions that include phosphorylation of Elk-1, constitutive regulation of c-Fos-DNA binding, TGFβ1 promoter transactivation, and TGFβ1 secretion. In addition, knockdown of km23-1 reduced the paracrine effects of CRC cell-secreted factors in conditioned medium and in fibroblast co-cultures. Moreover, km23-1 depletion in human CRC cells reduced cell migration and invasion, as well as expression of the ERK-regulated, metastasis-associated scaffold protein Ezrin. Finally, km23-1 inhibition significantly suppressed tumor formation in vivo. Thus, our results implicate km23-1 as a novel anti-metastasis target for human colon carcinoma cells, capable of decreasing tumor growth and invasion via a mechanism involving suppression of various pro-migratory features of CRC. These include a reduction in ERK signaling, diminished TGFβ1 production, decreased expression of the plasma membrane-cytoskeletal linker Ezrin, as well as attenuation of the paracrine effects of colon carcinoma-secreted factors on fibroblast migration and mitogenesis. As such, km23-1 inhibitors may represent a viable therapeutic strategy for interfering with colon cancer progression and invasion.

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Isolation and characterization of calcium sensing receptor null cells: A highly malignant and drug resistant phenotype of colon cancer

Cited by 29 publications

References 48 publications

Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype

Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype

Association between the expression of four upregulated miRNAs and extrathyroidal invasion in papillary thyroid carcinoma

Decreased Tumor Progression and Invasion by a Novel Anti-Cell Motility Target for Human Colorectal Carcinoma Cells

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