scholarly journals Stress-Inducible Gene Atf3 Dictates a Dichotomous Macrophage Activity in Chemotherapy-Enhanced Lung Colonization

2021 ◽  
Vol 22 (14) ◽  
pp. 7356
Author(s):  
Justin D. Middleton ◽  
Jared Fehlman ◽  
Subhakeertana Sivakumar ◽  
Daniel G. Stover ◽  
Tsonwin Hai
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Early Stage ◽  
Mechanistic Explanation ◽  
Host Cells ◽  
Secondary Site ◽  
Initial Increase ◽  
Cell Retention ◽  
Lung Colonization ◽  
Inducible Gene

Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung.

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

Early Detection of Cancer Using Smartphones

2021 ◽  
pp. 25-31
Author(s):  
Kodieswari A.
Keyword(s):  
Early Detection ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Early Detection Of Cancer ◽  
Early Stage ◽  
Circulating Tumor Cell ◽  
Efficient Technology ◽  
Abnormal Growth ◽  
High Death

Cancer disease is the second largest disease in the world with high death mortality. Cancer is an abnormal growth of a normal cell. There are more than 100 types of cancer like blood cancer, brain cancer, small intestine cancer, lung cancer, liver cancer, etc. The type of cancer can be classified by the type of cell which is initially affected. When cancer grows it does not show any symptom. The symptom will appear when the cancer cell grows in mass and the symptom of cancer depends on the type of cancer. The cause of cancers is environmental pollutants, food habits, inherited genetics, tobacco, stress, etc., but in practice, it is not possible to prove the cause of cancer since various cancers do not have specific fingerprints. After the heart attack, cancer is a second killer disease in India. The death mortality is high in cancer because in most of the cases it is identified at the final stage which causes more death. According to ICMR, among 1.27 billion Indian populations, the incidence of cancer is 70-90 per 100,000 populations and 70% of cancer is identified in the last stage accounting for high morality. There are many types of treatment to treat cancer and they are surgery, radiation therapy, chemotherapy, targeted therapy, hormone therapy, stem cell transplant, etc. All cancer treatments will have side effects and the treatments will help only if the cancer cells are identified at the early stage. So time factor is important in diagnosing of cancer cells; hence, early detection of cancer will reduce the mortality rate. This chapter proposed the early detection of cancer cells using image processing techniques by the structure of circulating tumor cell. Early detection of cancer cells is very difficult because the concentration of cancer cells are extremely small and about one million malignant cell is encountered per billion of healthy cells. The circulating tumor cells, CTC, are shed into the bloodstream as a tumor grows, and it is believed these cells initiate the spread of cancer. CTC are rare, existing as only a few per one billion blood cells, and a highly efficient technology like chip-based biosensor platforms is required to capture the CTC, which in turn helps to detect cancer cell at an early stage before spreading. In proposed method, the circulating tumor cell has used a marker to detect cancer at early stage.

scholarly journals Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition

2015 ◽  
Vol 6 (1) ◽  
pp. 237-245 ◽  
Author(s):  
Johannes Kreuzer ◽  
Nina C. Bach ◽  
Daniel Forler ◽  
Stephan A. Sieber
Keyword(s):  
Cell Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Mechanistic Explanation ◽  
Cancer Cell Growth ◽  
Target Discovery ◽  
Mechanism Of Growth

Using a chemical proteomic strategy we analyzed the targets of acivicin and provided a mechanistic explanation for its inhibition of cancer cell growth.

scholarly journals Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Donna M. Sosnoski ◽  
Venkatesh Krishnan ◽  
William J. Kraemer ◽  
Courtenay Dunn-Lewis ◽  
Andrea M. Mastro
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Host Cells ◽  
Bone Microenvironment ◽  
Intracardiac Injection ◽  
Cell Colonization

It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFPhuman metastatic breast cancer cells, MDA-MB-231BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization.

scholarly journals Design of MEMS-based Microfludic Channel to Detect Cancer Cells in Blood

2020 ◽  
Vol 11 (1) ◽  
pp. 561-566
Author(s):  
Syed Shameem ◽  
RamaKrishna T V ◽  
Sahithi M ◽  
Rohitha B ◽  
Keerthana J ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Early Stage ◽  
Microfluidic Channel ◽  
Cell Detection ◽  
Malignant Growth ◽  
Simple Manner ◽  
Abnormal Cells ◽  
Mass Displacement ◽  
Cancer Cell Detection

Cancer refers to any of countless infections characterized by the development of abnormal cells that divide uncontrollably and can invade and destroy normal body tissue. Malignant growth frequently can spread all through your body. Cancer is the second driving reason for death on the planet. In this paper, we propose to found a H-cell to screen carcinogenic cells in a given sample of blood based on the principle of diffusion. This model incorporates the planning of a MEMS-based microfluidic channel to screen and recognize different cells depending on the size and various characteristics of the cells. Some of the methods which are implemented not efficient models for cancer cells detection in blood. The mass, displacement technique has been implemented in this investigation for cancer cell detection, with the help of this achieves the accuracy and better throughput. One cancer cell contains = 1.70371e-24 mass, such that with a weight of this formula, find out the total no of cells in the blood. This is the best method compared to existed methods. Using this count, the weight has been calculate early-stage cancer and treatment with a simple manner, CTCs in the blood is the un potential matter for health, H-cells have been measured with proposed weight and force technique such that in this investigation also calculate the healthy and cancer cells also. Finally, using this methodology achieves 93.58% accuracy, 0.00124 MSE. These are very good results compared to conventional methods.

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

scholarly journals Deficiency of Ku Induces Host Cell Exploitation in Human Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Okay Saydam ◽  
Nurten Saydam
Keyword(s):  
Host Cell ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Therapy Resistance ◽  
Host Cells ◽  
Human Cancer Cells ◽  
Parasitic Lifestyle

Cancer metastasis is the major cause of death from cancer (Massague and Obenauf, 2016; Steeg, 2016). The extensive genetic heterogeneity and cellular plasticity of metastatic tumors set a prime barrier for the current cancer treatment protocols (Boumahdi and de Sauvage, 2020). In addition, acquired therapy resistance has become an insurmountable obstacle that abolishes the beneficial effects of numerous anti-cancer regimens (De Angelis et al., 2019; Boumahdi and de Sauvage, 2020). Here we report that deficiency of Ku leads to the exploitation of host cells in human cancer cell line models. We found that, upon conditional deletion of XRCC6 that codes for Ku70, HCT116 human colorectal cancer cells gain a parasitic lifestyle that is characterized by the continuous cycle of host cell exploitation. We also found that DAOY cells, a human medulloblastoma cell line, innately lack nuclear Ku70/Ku86 proteins and utilize the host-cell invasion/exit mechanism for maintenance of their survival, similarly to the Ku70 conditionally-null HCT116 cells. Our study demonstrates that a functional loss of Ku protein promotes an adaptive, opportunistic switch to a parasitic lifestyle in human cancer cells, providing evidence for a previously unknown mechanism of cell survival in response to severe genomic stress. We anticipate that our study will bring a new perspective for understanding the mechanisms of cancer cell evolution, leading to a shift in the current concepts of cancer therapy protocols directed to the prevention of cancer metastasis and therapy resistance.

Induction of tenascin in cancer cells by interactions with embryonic mesenchyme mediated by a diffusible factor

1993 ◽  
Vol 104 (2) ◽  
pp. 289-296 ◽  
Author(s):  
N. Hiraiwa ◽  
H. Kida ◽  
T. Sakakura ◽  
M. Kusakabe
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Culture Media ◽  
Human Cancer ◽  
Early Stage ◽  
Cancer Cell Lines ◽  
Epithelial Cancer ◽  
Human Cancer Cell Lines

Human cancer cell lines A431 and MCF7, which do not produce tenascin (TN) in vitro, were found to produce TN when injected into nude mice or co-cultured with the embryonic mesenchyme. The TN expression in the developing A431 solid tumor was demonstrated by immunohistochemistry and by in situ hybridization. Human TN was detected in culture media by western blot analysis using human specific monoclonal antibody (RCB-1). During tumorigenesis, in the early stage, mouse TN was actively induced and deposited in the peri- and intertumor spaces surrounding the developing tumor. Two days later, TN derived from human epithelial cancer cells was induced and mainly deposited in the intertumor basement membrane. After this stage, tumor cells were actively producing TN. On the other hand, TN induction in non TN-producing cells, such as A431 and MCF7 cell lines, was also observed in vitro. Although cell lines such as NIH-3T3, phi 2, STO, 2H6, 3E5 and CMT315, had no effect on the TN induction, primary cultured embryonic mesenchyme effectively stimulated the TN expression in the cancer cell lines. This mesenchymal effect decreased with age and was entirely lost postnatally. Furthermore, conditioned media from these embryonic mesenchymes could reproduce the same effects on TN induction as observed in the co-culture study. In conclusion, these findings suggest that TN induction in epithelial cancer cells may depend on interactions with the surrounding environment, that these interactions may be mediated by a soluble factor(s) derived from the surrounding mesenchyme and that the TN induction observed in the tumorigenesis may reflect histogenesis during the embryonic period.

scholarly journals Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis

2017 ◽  
Vol 114 (34) ◽  
pp. E7159-E7168 ◽  
Author(s):  
Yi Seok Chang ◽  
Swati P. Jalgaonkar ◽  
Justin D. Middleton ◽  
Tsonwin Hai
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Immune Modulation ◽  
Cancer Metastasis ◽  
Chemotherapeutic Agent ◽  
Host Cells ◽  
Inflammatory Monocytes ◽  
Metastatic Lung ◽  
Inducible Gene

Chemotherapy is a double-edged sword. It is anticancer because of its cytotoxicity. Paradoxically, by increasing chemoresistance and cancer metastasis, it is also procancer. However, the underlying mechanisms for chemotherapy-induced procancer activities are not well understood. Here we describe the ability of paclitaxel (PTX), a frontline chemotherapeutic agent, to exacerbate metastasis in mouse models of breast cancer. We demonstrate that, despite the apparent benefit of reducing tumor size, PTX increased the circulating tumor cells in the blood and enhanced the metastatic burden at the lung. At the primary tumor, PTX increased the abundance of the tumor microenvironment of metastasis, a landmark microanatomical structure at the microvasculature where cancer cells enter the blood stream. At the metastatic lung, PTX improved the tissue microenvironment (the “soil”) for cancer cells (the “seeds”) to thrive; these changes include increased inflammatory monocytes and reduced cytotoxicity. Importantly, these changes in the primary tumor and the metastatic lung were all dependent on Atf3, a stress-inducible gene, in the noncancer host cells. Together, our data provide mechanistic insights into the procancer effect of chemotherapy, explaining its paradox in the context of the seed-and-soil theory. Analyses of public datasets suggest that our data may have relevance to human cancers. Thus, ATF3 in the host cells links a chemotherapeutic agent—a stressor—to immune modulation and cancer metastasis. Dampening the effect of ATF3 may improve the efficacy of chemotherapy.

scholarly journals ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Li Li ◽  
Yijia Gong ◽  
Ke Xu ◽  
Weihong Chen ◽  
Jiuyi Xia ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Promoter Methylation ◽  
Early Stage ◽  
Cervical Cancer Cell ◽  
Potential Marker ◽  
Cervical Cancer Cells

Abstract Background Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. Methods Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. Results This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. Conclusion These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.

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