A Novel Way to Characterize the Non-Specific Surface Adhesion of Cancer Cells and Understand Cancer Metastasis

2009 ◽  
Author(s):  
Xin Tang ◽  
Tony Cappa ◽  
Theresa Kuhlenschmidt ◽  
Mark Kuhlenschmidt ◽  
Taher A. Saif
Keyword(s):  
Cancer Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Microelectromechanical Systems ◽  
Adhesion Force ◽  
Colon Adenocarcinoma ◽  
Force Sensor ◽  
Human Colon ◽  
Force Response ◽  
Tumor Spread

Cancer deaths are mostly caused by the metastasis of the malignant cells, not by the primary tumor itself. During metastasis, cancer cells detach from the primary tumor, spread to different tissues via blood circulation or lymph system, and reattach to invade new tissues and organs. In this project, we hypothesize that cancer cells manage their invasion by changing their surface adhesivity. To study the cell surface adhesivity, a novel and versatile microelectromechanical systems (MEMS) force sensor is developed to quantify the strength of adhesion between living cancer cells and a probe. The Silicon sensors consist of a probe and 2 flexible cantilever beams, while the probe is used to contact the cancer cell and the flexible beams are used to measure the cell force response in the range from nN to uN. The spring constant of the sensor is 14 nN/ μm. Our results demonstrate that the aggressive HCT-8 cells (from human colon adenocarcinoma) show high nonspecific adhesivity when they aggregate into cell islands, and low surface non-specific adhesivity after they disassociate from the cell islands. The surface adhesivity of less aggressive Caco-2 cells (from human colon carcinoma) and normal MA104 cell (from monkey kidney) are found to be lower than that of before-disassociation HCT-8 cells. Furthermore, the adhesion force response of cancer cells is found to show 2-slope force behavior, which is different from previous results of focal-adhesion detachment experiments. The 2-stage force bearing model is proposed to interpret the underlying mechanism.

Induction of Apoptic Features in Human Colon Cancer Cells After Exposure to Specific Vitamin Combinations

2000 ◽  
Vol 6 (S2) ◽  
pp. 892-893
Author(s):  
B. Brown ◽  
K. R. Garvin ◽  
B. G. Hughes ◽  
M. D. Standing ◽  
K. L. O'Neill ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Human Cancer Cells ◽  
Induction Of Apoptosis ◽  
Programed Cell Death ◽  
Ht 29

Proper nutrition and vitamin consumption have long been associated with lower risks for many human cancers. Data from recent studies have suggested that exposure to antioxidant vitamins and vitamin combinations can induce genetic programed cell death, apoptosis, in human cancer cells. ‘“3 In this study, we report on the induction of apoptosis in HT-29 human colon adenocarcinoma cells after exposure to low doses of 13- c/s-retinoic acid (RA) and vitamin E succinate (VES). Induction of apoptosis was seen only in cancerous colon cells and not in normal human colon cells when exposed to RA and VES in combination, but not when exposed to either vitamin alone.Cultures of HT-29 cells were seeded in 6 well plates at 10,000 cells/well and grown at 37°C, 5% C02 in RPMI 1640 medium supplemented with 10% fetal bovine serum.

scholarly journals Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

2015 ◽  
Vol 309 (7) ◽  
pp. C444-C456 ◽  
Author(s):  
Tsz-Lun Yeung ◽  
Cecilia S. Leung ◽  
Kay-Pong Yip ◽  
Chi Lam Au Yeung ◽  
Stephen T. C. Wong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Hematogenous Metastasis ◽  
Ovarian Cancer Cells ◽  
Molecular Processes ◽  
Lower Survival Rate ◽  
Gynecological Malignancy

Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the “seed-and-soil” hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

scholarly journals Subcellular distribution of ezrin/radixin/moesin and their roles in the cell surface localization and transport function of P-glycoprotein in human colon adenocarcinoma LS180 cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250889
Author(s):  
Takuro Kobori ◽  
Mayuka Tameishi ◽  
Chihiro Tanaka ◽  
Yoko Urashima ◽  
Tokio Obata
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Cancer Cells ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Membrane Localization ◽  
Transport Function ◽  
Erm Proteins ◽  
Plasma Membrane Localization ◽  
Surface Localization

The ezrin/radixin/moesin (ERM) family proteins act as linkers between the actin cytoskeleton and P-glycoprotein (P-gp) and regulate the plasma membrane localization and functionality of the latter in various cancer cells. Notably, P-gp overexpression in the plasma membrane of cancer cells is a principal factor responsible for multidrug resistance and drug-induced mutagenesis. However, it remains unknown whether the ERM proteins contribute to the plasma membrane localization and transport function of P-gp in human colorectal cancer cells in which the subcellular localization of ERM has yet to be determined. This study aimed to determine the gene expression patterns and subcellular localization of ERM and P-gp and investigate the role of ERM proteins in the plasma membrane localization and transport function of P-gp using the human colon adenocarcinoma cell line LS180. Using real-time reverse transcription polymerase chain reaction and immunofluorescence analyses, we showed higher levels of ezrin and moesin mRNAs than those of radixin mRNA in these cells and preferential distribution of all three ERM proteins on the plasma membrane. The ERM proteins were highly colocalized with P-gp. Additionally, we show that the knockdown of ezrin, but not of radixin and moesin, by RNA interference significantly decreased the cell surface expression of P-gp in LS180 cells without affecting the mRNA expression of P-gp. Furthermore, gene silencing of ezrin substantially increased the intracellular accumulation of rhodamine123, a typical P-gp substrate, with no alterations in the plasma membrane permeability of Evans blue, a passive transport marker. In conclusion, ezrin may primarily regulate the cell surface localization and transport function of P-gp as a scaffold protein without influencing the transcriptional activity of P-gp in LS180 cells. These findings should be relevant for treating colorectal cancer, which is the second leading cause of cancer-related deaths in males and females combined.

scholarly journals Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3550 ◽  
Author(s):  
Eleonora Mungo ◽  
Loredana Bergandi ◽  
Iris Salaroglio ◽  
Sophie Doublier
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Colon Adenocarcinoma ◽  
Glucose Consumption ◽  
Mitochondrial Respiratory Chain ◽  
Human Colon ◽  
Chemotherapeutic Agents ◽  
Cross Resistance ◽  
Ht29 Cells ◽  
Human Colon Adenocarcinoma

Emerging evidence supports the idea that a dysfunction in cell metabolism could sustain a resistant phenotype in cancer cells. As the success of chemotherapeutic agents is often questioned by the occurrence of multidrug resistance (MDR), a multiple cross-resistance towards different anti-cancer drugs represent a major obstacle to cancer treatment. The present study has clarified the involvement of the carbon metabolites in a more aggressive tumor colon adenocarcinoma phenotype and in a chemoresistant mesothelioma, and the role of pyruvate treatment in the reversion of the potentially related resistance. For the first time, we have shown that human colon adenocarcinoma cells (HT29) and its chemoresistant counterpart (HT29-dx) displayed different carbon metabolism: HT29-dx cells had a higher glucose consumption compared to HT29 cells, whereas human malignant mesothelioma (HMM) cells showed a lower glucose consumption compared to HT29 cells, accompanied by a lower pyruvate production and, consequently, a higher production of lactate. When treated with pyruvate, both HT29-dx and HMM cells exhibited a re-established accumulation of doxorubicin and a lower survival ability, a decreased activity of multidrug resistance protein 1 (MRP1) and a restored mitochondrial respiratory chain function, improving the effectiveness of the chemotherapeutic agents in these resistant cancer cells.

scholarly journals STAT6 mRNA and protein knockdown using multiple siRNA sequences inhibits proliferation and induces apoptosis of the human colon adenocarcinoma cell line, HT-29

2018 ◽  
Author(s):  
C. Salguero-Aranda ◽  
D. Sancho-Mensat ◽  
S. Sultan ◽  
A. Reginald ◽  
L. Chapman
Keyword(s):  
Cancer Cells ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Colorectal Cancers ◽  
Colon Cancer Cells ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Individual Sequences ◽  
Ht 29 ◽  
Human Colon Adenocarcinoma

AbstractThe transcription factor STAT6 is strongly expressed in various tumours and is most highly expressed in malignant lymphomas and pancreatic, colorectal, prostate and breast cancers. STAT6 expression in colorectal cancer is associated with an increased malignancy, poor prognosis and poor survival rates. Colorectal cancer has an incidence of approximately 1,361,000 patients per annum worldwide and approximately 60% of those cancers show STAT6 expression. Techniques aimed at reducing or blocking STAT6 expression may be useful in treating colorectal cancers. Celixir’s four proprietary STAT6 specific small interfering RNA (siRNA) sequences were tested in vitro using the human colon adenocarcinoma cell line, HT-29. The four sequences were introduced individually and in combination into HT-29 cells at different concentrations (10 to 200 nM). Decreases in STAT6 mRNA and protein levels were analysed to confirm the transfection was successful. STAT6 knockdown effects were measured by analysing cell proliferation and apoptosis. Results showed that 100nM siRNA concentration was the most effective and all four individual sequences knocked-down STAT6 mRNA and protein by more than 50%. Although all individual sequences were capable of significantly inhibiting cell proliferation, STAT6.1 and STAT6.4 were the best. STAT6 silencing also significantly induced late and total apoptotic events. In conclusion, these results demonstrate that STAT6 siRNA sequences are capable of inhibiting the proliferation, and inducing late apoptosis, of HT-29 colon cancer cells and, in some instances, halving the number of cancer cells. These experiments will be repeated using xenografts of STAT6-expressing colon cancer cells in immunocompromised mice and the STAT6 siRNA sequences will be tested in other cancers in which STAT6 is expressed. The STAT6 siRNA sequences therefore represent a potential treatment for the most serious colorectal cancers and a wide variety of STAT6-expressing cancers.

In Vitro Cancer Metastasis Induced by Mechanical Force

2013 ◽  
Author(s):  
Xin Tang ◽  
Taher Saif
Keyword(s):  
Cancer Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Mechanical Stimuli ◽  
Medicine Development ◽  
Secondary Tumors ◽  
Cancer Tumor ◽  
First Time ◽  
Critical Reason

Based on the American Cancer Society’s report at 2004, after 50-year’s efforts in bio-chemical medicine development, the U.S.A. cancer mortality is 193.9 per 100,000 persons, which is not significantly reduced from that at 1950, 185.8 per 100,000 persons. One critical reason for the clinical inefficacy is that it is not identified what signals trigger the onset of metastasis. 90% of cancer deaths are caused by metastases (1–6). During metastasis, malignant cancer cells detach from the parent cancer tumor to invade new organs (5–7). Although the primary tumor can be readily removed by surgery if detected in time, metastasis cannot be cured effectively due to the presence of numerous secondary tumors. Here we present, for the first time, that cancer cells can exhibit metastasis like phenotype (MLP) in vitro when they are experiencing appropriate mechanical stimuli.

scholarly journals A Link between FXYD3 (Mat-8)-mediated Na,K-ATPase Regulation and Differentiation of Caco-2 Intestinal Epithelial Cells

2009 ◽  
Vol 20 (4) ◽  
pp. 1132-1140 ◽  
Author(s):  
Stéphanie Bibert ◽  
David Aebischer ◽  
Florian Desgranges ◽  
Sophie Roy ◽  
Danièle Schaer ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cancer Cells ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Intestinal Epithelial ◽  
Differentiation Markers ◽  
Adenocarcinoma Cells ◽  
Human Colon Adenocarcinoma ◽  
Colon Adenocarcinoma Cells

FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is mainly expressed in stomach and colon, but it is also overexpressed in cancer cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no effect on cell proliferation but promotes cell apoptosis and prevents cell differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected by a reduction in alkaline phosphatase and villin expression, a change in several other differentiation markers, and a decrease in transepithelial resistance. Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in the maximal Na,K-ATPase activity due to a decrease in its turnover number, which correlates with a change in Na,K-ATPase isozyme expression that is characteristic of cancer cells. Overall, our results suggest an important role of FXYD3 in cell differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with Caco-2 cell differentiation.

scholarly journals Hormonal control of fructose 2,6-bisphosphate concentration in the HT29 human colon adenocarcinoma cell line α2-adrenergic agonists counteract effect of vasoactive intestinal peptide

1986 ◽  
Vol 239 (3) ◽  
pp. 531-536 ◽  
Author(s):  
C Denis ◽  
H Paris ◽  
J C Murat
Keyword(s):  
Cyclic Amp ◽  
Cancer Cells ◽  
Vasoactive Intestinal Peptide ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Hormonal Control ◽  
Maximum Effect ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Human Colon Adenocarcinoma

Vasoactive intestinal peptide (VIP) was found to cause a dose-dependent decrease in fructose 2,6-bisphosphatase concomitant with an increase in cyclic AMP in cultured HT29 cancer cells from human colon. The maximum effect was a 41% decrease obtained with 10 nM-VIP, and half-maximum effect was obtained with 0.75 nM-VIP. The effect of 2.5 nM-VIP was almost totally counteracted (i.e. fructose 2,6-bisphosphate concentration was restored) by either adrenaline (1 microM) or the alpha 2-adrenergic agonist UK-14304 (1 microM); the alpha 2-agonist clonidine (1 microM) was less efficient, since the VIP effect was decreased by 72% only. The adrenaline effect was totally antagonized by 1 microM-yohimbine. It is concluded that, in the HT29 cancer cells, the fructose 2,6-bisphosphate-producing system is sensitive to variations of cyclic AMP concentration and is under the dual control of VIP and alpha 2-adrenergic receptors.

Studying the Mechanical Sensitivity of Human Colon Cancer Cells Through a Novel Bio-MEMS Force Sensor

2010 ◽  
Author(s):  
Xin Tang ◽  
Tony Cappa ◽  
Theresa B. Kuhlenschmidt ◽  
Mark S. Kuhlenschmidt ◽  
Taher A. Saif
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Circulatory System ◽  
Force Sensor ◽  
Human Colon ◽  
Underlying Mechanism ◽  
Mechanical Stiffness ◽  
Human Colon Cancer ◽  
Microscopy Imaging

Cancer deaths are primarily caused by metastases, not by the parent tumor. During the metastasis, malignant cancer cells detach from the parent tumor, and spread through the patient’s circulatory system to invade new tissues and organs [1]. To study the role played by the mechanical microenvironment on the cancer cell growth and malignancy promotion, we cultured human colon carcinoma (HCT-8) cells in vitro on substrates with varied mechanical stiffness, from the physiologically relevant 1 kPa, 20 kPa to very stiff 3.5 GPa. A novel and versatile micro-electromechanical systems (Bio-MEMS) force sensor [2] is developed to quantify the strength of non-specific adhesion between living cancer cells membrane and probe, an important hallmark of cancer cell malignancy level. Immunoflurescent staining and Confocal microscopy imaging are used to visualize the cellular organelle organization and cooperate to explore the underlying mechanism.

ADHESIVITY OF COLON CANCER CELLS DURING IN VITRO METASTASIS

2013 ◽  
Vol 05 (03) ◽  
pp. 1350025 ◽  
Author(s):  
XIN TANG ◽  
TAHER A. SAIF
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Force Sensor ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Surface Adhesion ◽  
Soft Substrate ◽  
Human Colon Carcinoma ◽  
Cancer Cell Adhesion

Human colon carcinoma (HCT-8) cells show a stable, metastasis-like phenotype (MLP) when cultured on appropriate soft substrates (21 ~ 47 kPa). Initially epithelial (E) in nature, the HCT-8 cells become rounded (R) and show a number of metastatic hallmarks after only seven days of culture on soft substrate (Tang et al., [2010] "Mechanical force affects expression of an in vitro metastasis-like phenotype in HCT-8 cells," Biophysical Journal99, 2460–2469; Tang et al., [2012a] "Attenuation of cell mechanosensitivity in colon cancer cells during in vitro metastasis," PlosONE7, e50443). Here, we studied the surface nonspecific adhesion of HCT-8 cells throughout the in vitro metastasis process. A novel bio-MEMS force sensor was used to measure the cell-probe nonspecific adhesion. The adhesion characteristics are analyzed using fracture mechanics theory. Our results indicate that the post-metastatic HCT-8 cells (dissociated R cells) display remarkably diminished surface adhesion and are potentially more invasive than original pre-metastatic HCT-8 cells (E cells). To the best of our knowledge, this is the first report of quantitative data showing the changes in cancer cell adhesion and other cellular mechanical properties during the expression of in vitro metastasis-like phenotype.

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