The study of molecular signals and the immune
system behavior in cancer cell metastasis:
A literature review

Relevance: This study’s relevance is due to the lack among academia of a holistic picture of the processes that occur in the body in cancer cell metastasis. Particularly, a lot is unclear about the physical mechanism of molecular signaling and organizing immune responses, as well as registering the frequency and amplitude of ultra-weak electromagnetic signals with the development of a tumor process in the body. The purpose of this study was to review the literature sources regarding the physicochemical mechanisms of processes that occur in the body in cancer cell metastasis. Results: The analysis of the selected sources gives reason to believe that a medico-biological point of view is not enough to explain tumor metastasis. The mentioned sources highlight the issues related to the physical and chemical components of this process. The publications state the facts of the reorganization of cancer cells at receiving molecular signals. Hence, the authors do not explain what structures form molecular signals of a strictly defined frequency and how physically the cancer cell receives these signals and implements them into practical responses. It is evident that these molecular signals are ultra-weak electromagnetic waves. Methods of quantification of some parameters of the metastasis process are proposed, as well as the ways to register ultra-weak electromagnetic signals. Conclusion: Data on the physicochemical mechanisms of various stages of metastasis of malignant tumors included in this review complements the picture of the process of cancer metastasis in the human body and defines a range of issues that require interdisciplinary research involving both physicians and biologists, and specialists in quantum physics, electronics, and chemistry. Only quantum electrodynamics can explain the mechanism of a cell cytoskeleton transformation (from a healthy to a tumor cell) under the influence of weak electromagnetic signals. The authors reveal priority directions for an interdisciplinary study of bioenergetic processes that occur in the body in cancer cell metastasis.

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A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

International Journal of Molecular Sciences ◽

10.3390/ijms19123968 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3968 ◽

Cited By ~ 17

Author(s):

Enrico Spugnini ◽

Mariantonia Logozzi ◽

Rossella Di Raimo ◽

Davide Mizzoni ◽

Stefano Fais

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

The Body ◽

Mesenchymal Transition ◽

Metastatic Cascade ◽

Target Organs

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

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Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/732578 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

Chih-Yu Peng ◽

Hui-Wen Yang ◽

Yin-Hung Chu ◽

Yu-Chao Chang ◽

Ming-Ju Hsieh ◽

...

Keyword(s):

Oral Cancer ◽

Matrix Metalloproteinase ◽

Caffeic Acid ◽

Cancer Cell ◽

Cancer Metastasis ◽

Caffeic Acid Phenethyl Ester ◽

Matrix Metalloproteinase 2 ◽

Migration And Invasion ◽

Oral Cancer Cell ◽

Cell Metastasis

Caffeic acid phenethyl ester (CAPE), an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM). Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2) protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and potently decreased migration by reducing focal adhesion kinase (FAK) phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.

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PSY-1, a Taxus chinensis var. mairei Extract, Inhibits Cancer Cell Metastasis by Interfering with MMPs

Natural Product Communications ◽

10.1177/1934578x1400900228 ◽

2014 ◽

Vol 9 (2) ◽

pp. 1934578X1400900 ◽

Cited By ~ 1

Author(s):

Zao-qian Zheng ◽

Ying-Ying Fu ◽

Bo-Heng Li ◽

Mei-Ling Zhang ◽

Xiu-Li Yang ◽

...

Keyword(s):

Cancer Cell ◽

Cancer Metastasis ◽

Cancer Cell Line ◽

Water Soluble ◽

Migration And Invasion ◽

Common Disease ◽

Taxus Chinensis ◽

Cancer Treatments ◽

Melanoma Cancer ◽

Cell Metastasis

Cancer is the most common disease worldwide, with death often occurring as a result of metastasis. Thus, interfering with metastasis has been regarded as a promising strategy to improve the current cancer treatments. However, exploration and development of novel anti-metastatic agents remains a major challenge. Recent evidence indicated that a polysaccharide isolated from Taxus yunnanensis suppressed tumor cells proliferation. With the objective of seeking bioactive extracts, we had previously isolated, purified and characterized a complex, water-soluble polysaccharides, PSY-1, from the leaves of Taxus chinensis var. mairei, and identified its anti-neoplastic effects. In this study, we focused on the effects of PSY-1 on cancer metastasis and its mechanism(s). The results illustrated that PSY-1 effectively suppressed the migration and invasion ability of the melanoma cancer cell line B16-F10, caused down-regulation of MMP-2 and MMP-9, and that the NF-κB pathway was involved in the anti-metastatic effects imposed by PSY-1.

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The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial–mesenchymal transition

Cancer Cell International ◽

10.1186/s12935-021-01841-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yaoyao Xiong ◽

Xiongbing Zu ◽

Long Wang ◽

Yuan Li ◽

Minfeng Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Bladder Cancer Cell ◽

Mesenchymal Transition ◽

Metastatic Bladder Cancer ◽

Cell Metastasis ◽

Bladder Cancer Cells

Abstract Background Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial–mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. Methods Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. Results Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. Conclusions In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.

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NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay

Oncogene ◽

10.1038/s41388-021-01900-8 ◽

2021 ◽

Author(s):

Lin Zhao ◽

Longyang Jiang ◽

Ming Zhang ◽

Qiang Zhang ◽

Qiutong Guan ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cell ◽

Mrna Stability ◽

Mrna Decay ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Breast And Ovarian Cancer ◽

Cell Metastasis

AbstractPrevious study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3′-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3′-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3′-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.

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Cancer cell metastasis; perspectives from the focal adhesion

Advances in Modern Oncology Research ◽

10.18282/amor.v1.i1.6 ◽

2015 ◽

Vol 1 (1) ◽

pp. 2

Author(s):

Lefteris C Zacharia ◽

Vasiliki Gkretsi

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Primary Tumor ◽

Critical Role ◽

The Body ◽

Cancer Tissue ◽

Human Breast Cancer Tissue ◽

Cell Metastasis

<p class="BodyText1">In almost all cancers, most patients die from metastatic disease and not from the actual primary tumor. That is why addressing the problem of metastasis is of utmost importance for the successful treatment and improved survival of cancer patients. Metastasis is a complex process that ultimately leads to cancer cells spreading from the tumor to distant sites of the body. During this process, cancer cells tend to lose contact with the extracellular matrix (ECM) and neighboring cells within the primary tumor, and are thus able to invade surrounding tissues. Hence, ECM, and the ECM-associated adhesion proteins play a critical role in the metastatic process. This review will focus on recent literature regarding interesting and novel molecules at the cell-ECM adhesion sites, namely migfilin, mitogen-inducible gene-2 (Mig-2) and Ras suppressor-1 (RSU-1), that are also critically involved in cancer cell metastasis, emphasizing on data from experiments performed in vitro in breast cancer and hepatocellular carcinoma cell lines as well as human breast cancer tissue samples.</p>

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Beyond Neurons: Long Distance Communication in Development and Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.739024 ◽

2021 ◽

Vol 9 ◽

Author(s):

Patrick McMillen ◽

Madeleine J. Oudin ◽

Michael Levin ◽

Samantha L. Payne

Keyword(s):

Communication Networks ◽

Electric Fields ◽

Cancer Metastasis ◽

Single Cells ◽

Electrical Coupling ◽

The Body ◽

Molecular Signaling ◽

Tunneling Nanotubes ◽

Long Distance ◽

Distance Communication

Cellular communication is important in all aspects of tissue and organism functioning, from the level of single cells, two discreet populations, and distant tissues of the body. Long distance communication networks integrate individual cells into tissues to maintain a complex organism during development, but when communication between cells goes awry, disease states such as cancer emerge. Herein we discuss the growing body of evidence suggesting that communication methods known to be employed by neurons, also exist in other cell types. We identify three major areas of long-distance communication: bioelectric signaling, tunneling nanotubes (TNTs), and macrophage modulation of networks, and draw comparisons about how these systems operate in the context of development and cancer. Bioelectric signaling occurs between cells through exchange of ions and tissue-level electric fields, leading to changes in biochemical gradients and molecular signaling pathways to control normal development and tumor growth and invasion in cancer. TNTs transport key morphogens and other cargo long distances, mediating electrical coupling, tissue patterning, and malignancy of cancer cells. Lastly macrophages maintain long distance signaling networks through trafficking of vesicles during development, providing communication relays and priming favorable microenvironments for cancer metastasis. By drawing comparisons between non-neural long distance signaling in the context of development and cancer we aim to encourage crosstalk between the two fields to cultivate new hypotheses and potential therapeutic strategies.

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Ultrasonic differential diagnostics of cyst and cystic tumors of the spleen

Medical Visualization ◽

10.24835/1607-0763-2020-3-63-75 ◽

2020 ◽

Vol 24 (3) ◽

pp. 63-75

Author(s):

Yu. A. Stepanova ◽

M. Z. Alimurzaeva ◽

D. A. Ionkin

Keyword(s):

Differential Diagnosis ◽

Cancer Metastasis ◽

Malignant Tumors ◽

Dynamic Control ◽

Differential Diagnostics ◽

Epithelial Lining ◽

Focal Lesions ◽

Morphological Form ◽

Cystic Tumors ◽

Number Of Patients

The incidence of focal lesions in the spleen is 3.2–4.2% per 100,000 population. Spleen cysts are rare (incidence 0.75 per 100,000). These are single or multiple, thin- and smooth-walled cavities filled with a transparent liquid. Distinguish between primary (or true) cysts, lined with epithelium, and secondary (or false), devoid of epithelial lining. Among the primary cysts, there are congenital cysts formed in the embryonic period due to the migration of peritoneal cells into the spleen tissue, dermoid and epidermoid cysts. A special group of primary cysts are parasitic cysts. Cystic tumors of the spleen include lymphangioma and lymphoma.The main difficulties in the diagnosis and differential diagnosis of cysts and cystic tumors of the spleen are associated with the rarity of this pathology and, as a consequence, a small number of works, including a significant number of the cases. However, in those works where a large number of the cases are described, most often this is one morphological form and an analysis of its various characteristics.Purpose. Based on the analysis of our own examination data of a significant number of patients with cysts and cystic tumors of the spleen, to assess the possibility of differential diagnosis of individual morphological forms according to ultrasound data.Materials and methods. 323 patients with cysts and cystic tumors of the spleen from 15 to 77 years old (men – 105 (32.5%); women – 218 (67.5%) were treated at A.V. Vishnevsky National Medical Research Center of Surgery for the period from 1980 to 2020. All patients underwent ultrasound during examination. Surgical treatment was carried out in various ways – (85.1%), when making a preoperative diagnosis of an uncomplicated spleen cyst of small size, dynamic observation was carried out (verification by puncture biopsy data).Results. Morphological verification of cysts and cystic tumors of the spleen was presented as follows (taking into account possible difficulties in identifying the epithelial lining): true cyst – 182 (56.4%); dermoid cyst – 3 (0.9%) (malignant – in 1 case); pseudocyst – 16 (5.0%); pancreatogenic – 34 (10.5%); echinococcus – 52 (16.1%); lymphangioma – 24 (7.4%); lymphoma – 10 (3.1%); ovarian cancer metastasis – 2 (0.6%). The article describes the ultrasound signs of the above forms of the lesions with an emphasis on the complexity of diagnosis.Conclusions. Primary and parasitic spleen cysts are well differentiated according to ultrasound; false cysts of the spleen, depending on the cause of their occurrence, can create difficulties in their identification and differentiation (they require careful dynamic control); cystic tumors of the spleen should be differentiated from malignant tumors and metastases of a cystic structure, as a result of which such vigilance should always be present when they are detected.

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REPEATED LONG-TERM SPACE FLIGHTS: PROTEOMIC INVESTIGATIONS OF COSMONAUTS' BLOOD

Aerospace and Environmental Medicine ◽

10.21687/0233-528x-2020-54-5-15-22 ◽

2020 ◽

Vol 54 (5) ◽

pp. 15-22

Author(s):

I.M. Larina ◽

◽

D.N. Kashirina ◽

K.S. Kireev ◽

A.I. Grigoriev ◽

...

Keyword(s):

Bone Structure ◽

Space Station ◽

The Body ◽

Coagulation Cascade ◽

Chemical Components ◽

Blood Proteins ◽

Blood Indices ◽

Before And After ◽

Biochemical Indices

We performed the first ever comparative analysis of modifications in the proteome, ionogram and some other blood plasma biochemical indices of 18 male cosmonauts (44 ± 6 years of age) before and after maiden or repeated long-term missions to the Russian segment of the International space station (ISS RS). Levels of proteins, substrates and ions as well as chemical components were measured using the LC-MS-based proteomics and routine biochemical techniques. A total of 256 to 281 indices were investigated with the methods of descriptive statistic, regression analysis, and access to bioinformatics resources. It was shown that blood indices recovery from the maiden and repeated missions reflects changes in the body systems and goes at a various speed. The results of measurements made prior to launch and on day 7 after landing are dependent on the number of missions. The bioinformatics techniques showed that after maiden missions both the mediator proteins of alkaline phosphatase (AP) and blood proteins with reliably changing concentrations are associated with the bio-processes including stress, metabolism and DNA reparation, apoptosis, catabolism and proteolysis. During early re-adaptation from repeated missions the AP level was affected by bone remodeling, phosphorylation, angiogenesis and coagulation cascade suggesting a distinct and urgent trigger of the processes of bone structure and mineralization.

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Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70S6K signaling pathway

Scientific Reports ◽

10.1038/s41598-021-85675-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sutthaorn Pothongsrisit ◽

Kuntarat Arunrungvichian ◽

Yoshihiro Hayakawa ◽

Boonchoo Sritularak ◽

Supachoke Mangmool ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Protein Kinase ◽

Small Cell Lung Cancer ◽

Cancer Metastasis ◽

Small Cell ◽

Migration And Invasion ◽

Lung Cancer Cell ◽

Small Cell Lung ◽

Cell Metastasis

AbstractCancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

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