Ultrastructural modification of cellular interactions in cancer tumor

One of the most characteristic features of cancer cells is their ability to metastasia. It is suggested that the modifications of the structure and properties of cancer cells surfaces play the main role in this process. The present work was aimed at finding out what ultrastructural features apear in tumor in vivo which removal of individual cancer cells from the cell population can provide. For this purpose the cellular interactions in the normal human thyroid and cancer tumor of this gland electron microscopic were studied. The tissues were fixed in osmium tetroxide and were embedded in Araldite-Epon.In normal human thyroid the most common type of intercellular contacts was represented by simple junction formed by the parallelalignment of adjacent cell membranees leaving in between an intermembranes space 15-20 nm filled with electronlucid material (Fig. 1a). Sometimes in the basal part of cells dilatations of the intercellular space 40-50 nm wide were found (Fig. 1a). Here the cell surfaces may form single short microvilli.

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Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

International Journal of Molecular Sciences ◽

10.3390/ijms22115930 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5930

Author(s):

Catharina Melzer ◽

Juliane von der Ohe ◽

Tianjiao Luo ◽

Ralf Hass

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Tumor Development ◽

Cellular Interactions ◽

Hybrid Cells ◽

Induced Tumors ◽

Culture Model ◽

Gene Expression Levels

Direct cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.

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Role of miRNAs in Breast Cancer-induced Bone Disease

Osteologie/Osteology ◽

10.1055/a-1514-1618 ◽

2021 ◽

Vol 30 (03) ◽

pp. 211-221

Author(s):

Marie-Therese Haider ◽

Jennifer Zarrer ◽

Daniel J. Smit ◽

Eric Hesse ◽

Hanna Taipaleenmäki

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Bone Remodeling ◽

Cancer Recurrence ◽

Bone Cancer ◽

Metastatic Tumor ◽

Cell Types ◽

Cellular Interactions

AbstractBone is the most common site of breast cancer recurrence. Despite the increasing knowledge about the metastatic process and treatment advances, the disease still remains incurable once the cancer cells actively proliferate in bone. Complex interactions between cancer cells and cells of the bone microenvironment (BME) regulate the initiation and progression of metastatic tumor growth in bone. In particular, breast cancer cells shift the otherwise tightly balanced bone remodeling towards increased bone resorption by osteoclasts. Cellular interactions in the metastatic BME are to a large extent regulated by secreted molecules. These include various cytokines as well as microRNAs (miRNAs), small non-coding RNAs that post transcriptionally regulate protein abundance in several cell types. Through this mechanism, miRNAs modulate physiological and pathological processes including bone remodeling, tumorigenesis and metastasis. Consequently, miRNAs have been identified as important regulators of cellular communication in the metastatic BME. Disruption of the crosstalk between cancer cells and the BME has emerged as a promising therapeutic target to prevent the establishment and progression of breast cancer bone metastasis. In this context, miRNA mimics or antagonists present innovative therapeutic approaches of high potential for interfering with pathological bone – cancer cell interactions. This review will discuss the role of miRNAs in the tumor-BME crosstalk in vivo and will emphasize how this could be targeted by miRNAs to improve therapeutic outcome for patients with breast cancer bone metastases.

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Cyclin D1b induces changes in the macrophage phenotype resulting in promotion of tumor metastasis

Experimental Biology and Medicine ◽

10.1177/15353702211038511 ◽

2021 ◽

pp. 153537022110385

Author(s):

Yuxue Wang ◽

Yi Liu ◽

Lei Xiang ◽

Lintao Han ◽

Xiaowei Yao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Selective Advantage ◽

Macrophage Phenotype ◽

Tumor Associated Macrophages ◽

Cancer Tumor ◽

Aggressive Breast Cancer

In breast cancer, tumor-associated macrophages with activated phenotypes promote tumor invasion and metastasis. The more aggressive mesenchymal-like breast cancer cells have a selective advantage, skewing macrophages toward the more immunosuppressive subtype. However, the mechanism underlying this shift is poorly understood. Cyclin D1b is a highly oncogenic variant of cyclin D1. Our previous study showed that non-metastatic epithelial-like breast cancer cells were highly metastatic in vivo when cyclin D1b was overexpressed. The present study determined whether cyclin D1b contributed to the interaction between breast cancer cells and macrophages. The results showed that cyclin D1b promoted the invasion of breast cancer cells in vitro. Specifically, through overexpression of cyclin D1b, breast cancer cells regulated the differentiation of macrophages into a more immunosuppressive M2 phenotype. Notably, tumor cells overexpressing cyclin D1b activated macrophages and induced migration of breast cancer cells. Further investigations indicated that SDF-1 mediated macrophage activation through breast cancer cells overexpressing cyclin D1b. These results revealed a previously unknown link between aggressive breast cancer cells and Tumor-associated macrophages, and highlighted the importance of cyclin D1b activity in the breast cancer microenvironment.

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IN-VITRO STUDIES OF NORMAL HUMAN THYROID CELLS: RESPONSES TO THYROTROPHIN AND DIBUTYRYL CYCLIC AMP

Journal of Endocrinology ◽

10.1677/joe.0.0720087 ◽

1977 ◽

Vol 72 (1) ◽

pp. 87-96 ◽

Cited By ~ 12

Author(s):

S. P. BIDEY ◽

P. MARSDEN ◽

J. ANDERSON ◽

C. G. McKERRON ◽

H. BERRY

Keyword(s):

Cyclic Amp ◽

Thyroid Tissue ◽

Three Dimensional ◽

Human Thyroid ◽

Dibutyryl Cyclic Amp ◽

Iodide Uptake ◽

Thyroid Cells ◽

Normal Human

SUMMARY Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the 'classical' TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this finding are discussed.

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IL-24-armed oncolytic vaccinia virus exerts potent antitumor effects via multiple pathways in colorectal cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x15942028641011 ◽

2020 ◽

Author(s):

Lili Deng ◽

Xue Yang ◽

Jun Fan ◽

Yuedi Ding ◽

Ying Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Vaccinia Virus ◽

Cancer Cells ◽

Treatment Options ◽

Antitumor Effects ◽

Colorectal Cancer Cells ◽

Cancer Tumor ◽

Induced Apoptosis

Colorectal cancer is an aggressive malignancy for which there are limited treatment options. Oncolytic vaccinia virus isbeing developed as a novel strategy for cancer therapy. Arming vaccinia virus with immunostimulatory cytokines can enhance the tumor cell-specific replication and antitumor efficacy. Interleukin-24 (IL-24) is an important immune mediator, as well as a broad-spectrum tumor suppressor. Here, we constructed a targeted vaccinia virus of Guang9 strain harbored IL-24 (VG9-IL-24) to evaluate its antitumor effects. In vitro, VG9-IL-24 induced increased number of apoptotic cells and blocked colorectal cancer cells in the G2/M phase of the cell cycle. VG9-IL-24 induced apoptosis in colorectal cancer cells via multiple apoptotic signaling pathways. In vivo,VG9-IL-24 significantly inhibited the tumor growth and prolonged the survival both in human and murine colorectal cancer models. Besides, VG9-IL-24 stimulated multiple antitumor immune responses and direct bystander antitumor activity. Our results indicate that VG9-IL-24 can inhibit the growth of colorectal cancer tumor by inducing oncolysis and apoptosis as well as stimulating the anti-tumor immune effects. These findings indicate that VG9-IL-24 may exert a potential therapeutic strategy for combating colorectal cancer

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Delving KS-01 as a Novel Therapeutic Strategy in Treating Breast Cancer

Journal of Global Oncology ◽

10.1200/jgo.18.29900 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 61s-61s

Author(s):

S.T. Saha ◽

M. Kaur

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Growth Inhibition ◽

Cancer Cells ◽

Breast Cancer Cell ◽

Cholesterol Accumulation ◽

Cholesterol Levels ◽

Normal Human

Background: Cancer cells have an increased need for cholesterol, which is required for cell membrane integrity. Cholesterol accumulation has been described in various malignancies including breast cancer. Cholesterol has also been known to be the precursor of estrogen and vitamin D, both of which play a key role in the histology of breast cancer. Thus, depleting the cholesterol levels in cancer cells is a proposed innovative strategy to treat cancer. Therefore, novel cholesterol-depleting compounds are currently being investigated. KS-01 is a cyclic amylose oligomer composed of glucose units. It solubilizes the cholesterol and is proven to be toxicologically benign in humans. Aim: To deplete cholesterol from cancer cells and investigating KS-01 to be a clinically useful compound. Our work provides preliminary experimental evidences to support this hypothesis. Methods: MTT assay (growth inhibition) APO percentage assay (apoptosis) Western blotting (protein expression) MOMP assay (mitochondrial membrane potential for apoptosis) Caspase 3,7 assay (caspase 3,7 activity for apoptosis) Cholesterol assay (to check cholesterol levels) RT-PCR (gene expression). Results: We identified the potency of KS-01 in vitro against two breast cancer cell lines: MCF-7 (estrogen positive, ER+), MDA-MB-231 (estrogen negative, ER-) and compared the results against two normal cell lines: MRC-5 (normal human lung fibroblasts) and HEK-293 (normal human embryonic kidney cells) using cytotoxic, apoptosis, protein expression and cholesterol based assays. KS-01 treatment reduced intracellular cholesterol resulting in significant breast cancer cell growth inhibition through apoptosis. The results hold true for both ER+ and ER-. Conclusion: The data obtained from our experiments suggest that KS-01 can prevent cholesterol accumulation in breast cancer cells and is a promising new anticancer agent. We are currently testing our hypothesis in vivo to validate the in vitro results. N.B: We have submitted the preliminary data to WITS ENTERPRISE (university's internal patenting agency). Once we get our in vivo data, the compound would be patented for its mechanism of action in breast cancer.

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Precise Engineering of Cisplatin Prodrug Into Supramolecular Nanoparticles: Enhanced on in Vitro Antiproliferative Activity and Treatment and Care of in Vivo Renal Injury

10.21203/rs.3.rs-254827/v1 ◽

2021 ◽

Author(s):

Zhenyun Zhou ◽

Xiaoxiao Chen

Keyword(s):

Cancer Cells ◽

Anticancer Drug ◽

Clinical Care ◽

Kidney Tissue ◽

Cost Effective ◽

Electron Microscopic ◽

Anticancer Properties ◽

Cost Effective Method

Abstract Renal cell carcinoma (RCC) is a widespread type of urological tumor that derives from the highly heterogeneous epithelium of the kidney tissue. For the past decade, the treatment of kidney cancer cells has changed clinical care for RCC. Herein, we present a very easy and cost-effective method that incorporates tumor-specific targeting supramolecular nanoassembly, and therapeutically to overcome the different challenges raised by the distribution of the pharmaceutical potential anticancer drug Cisplatin (CIS-PT). On covalent conjugations of hydrophobic linoleic acid by carboxylic group, the CIS-PT prodrugs were skilled in impulsively nanoassembly into extremely steady nanoparticles size (~100 nm). Electron microscopic techniques have verified the newly synthesized morphology of CIS-PT-NPs. The anticancer properties of CIS-PT and CIS-PT-NPs against Caki-1 and A-498 (renal carcinoma) cancer cell lines have been evaluated after successful synthesis. Other research, such as dual staining acridine orange/ethidium bromide, Hoechst 33344 and flow cytometry study on the apoptosis mechanisms, have shown that proliferation in renal cancer cells is associated with apoptosis. Further the In vivo toxicity results displays the CIS-PT-NPs remarkably alleviated the toxicity of the potential anticancer drug CIS-PT In vivo while conserving the Pharmaceutical activity. Compared to CIS-PT, CIS-PT-NPs demonstrate excellent In vitro and In vivo property, this study clarified the CIS-PT-NPs as a healthy and positive RCC care chemotherapeutics technique and deserve further clinical evaluations.

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CRSP8 promotes thyroid cancer progression by antagonizing IKKα-induced cell differentiation

Cell Death and Differentiation ◽

10.1038/s41418-020-00656-0 ◽

2020 ◽

Author(s):

Yina Liao ◽

Yijun Hua ◽

Yizhuo Li ◽

Changlin Zhang ◽

Wendan Yu ◽

...

Keyword(s):

Thyroid Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Direct Interaction ◽

Anaplastic Thyroid Cancer ◽

Human Thyroid ◽

Induced Apoptosis ◽

Thyroid Cancer Cells

Abstract CRSP8 plays an important role in recruiting mediators to genes through direct interaction with various DNA-bound transactivators. In this study, we uncovered the unique function of CRSP8 in suppressing thyroid cancer differentiation and promoting thyroid cancer progression via targeting IKKα signaling. CRSP8 was highly expressed in human thyroid cancer cells and tissues, especially in anaplastic thyroid cancer (ATC). Knockdown of CRSP8 suppressed cell growth, migration, invasion, stemness, and induced apoptosis and differentiation in ATC cells, while its overexpression displayed opposite effects in differentiated thyroid cancer (DTC) cells. Mechanistically, CRSP8 downregulated IKKα expression by binding to the IKKα promoter region (−257 to −143) to negatively regulate its transcription. Knockdown or overexpression of IKKα significantly reversed the expression changes of the differentiation and EMT-related markers and cell growth changes mediated by CRSP8 knockdown or overexpression in ATC or DTC cells. The in vivo study also validated that CRSP8 knockdown inhibited the growth of thyroid cancer by upregulating IKKα signaling in a mouse model of human ATC. Furthermore, we found that CRSP8 regulated the sensitivity of thyroid cancer cells to chemotherapeutics, including cisplatin and epirubicin. Collectively, our results demonstrated that CRSP8 functioned as a modulator of IKKα signaling and a suppressor of thyroid cancer differentiation, suggesting a potential therapeutic strategy for ATC by targeting CRSP8/IKKα pathway.

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IODOTHYRONINE CONTENT OF HUMAN THYROID ALBUMIN

Acta Endocrinologica ◽

10.1530/acta.0.0810288 ◽

1976 ◽

Vol 81 (2) ◽

pp. 288-297

Author(s):

Colette Thomas-Morvan

Keyword(s):

Thyroid Hormones ◽

Gel Electrophoresis ◽

Thyroid Tissue ◽

Iodine Concentration ◽

Human Thyroid ◽

Human Thyroid Tissue ◽

Normal Human ◽

The Difference ◽

Radioactive Measurement

ABSTRACT Stable thyroid hormones (T4 and T3)1) have been demonstrated in pure albumin isolated from normal human thyroid tissue iodinated in vivo. Five samples of albumin were separated from other thyroid proteins by acrylamide gel electrophoresis. After pronase hydrolysis, the content of Thyroid hormones was measured chemically (T4 + T3) as well as by competitive radioactive measurement (T4) and radioimmunoassay (T3). The purity of the albumin and validity of these measurements were confirmed by different techniques. The synthesis of thyroid hormones is not therefore a property unique to Tg and may occur in albumin. However the amount of iodothyronines in the albumin (average 0.004 residue per molecule) is much less than that found in Tg (0.5 residue per molecule). In the albumin as in Tg the number of hormone residues per molecule is proportional to the number of atoms of iodine. At an equivalent iodine concentration, the albumin seems capable of forming the thyroid hormones as well as Tg. The difference between these two proteins, in their capacity to synthesize thyroid hormones, seems to depend on their capacity for iodination. This difference of iodination does not seem to be linked with the number of tyrosyl residues, but might be related to the position of these residues.

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