scholarly journals The In Vivo Selection Method in Breast Cancer Metastasis

2021 ◽  
Vol 22 (4) ◽  
pp. 1886
Author(s):  
Jun Nakayama ◽  
Yuxuan Han ◽  
Yuka Kuroiwa ◽  
Kazushi Azuma ◽  
Yusuke Yamamoto ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Expression Patterns ◽  
Selection Method ◽  
Gene Signatures ◽  
In Vivo Selection ◽  
Metastatic Cancer Cells

Metastasis is a complex event in cancer progression and causes most deaths from cancer. Repeated transplantation of metastatic cancer cells derived from transplanted murine organs can be used to select the population of highly metastatic cancer cells; this method is called as in vivo selection. The in vivo selection method and highly metastatic cancer cell lines have contributed to reveal the molecular mechanisms of cancer metastasis. Here, we present an overview of the methodology for the in vivo selection method. Recent comparative analysis of the transplantation methods for metastasis have revealed the divergence of metastasis gene signatures. Even cancer cells that metastasize to the same organ show various metastatic cascades and gene expression patterns by changing the transplantation method for the in vivo selection. These findings suggest that the selection of metastasis models for the study of metastasis gene signatures has the potential to influence research results. The study of novel gene signatures that are identified from novel highly metastatic cell lines and patient-derived xenografts (PDXs) will be helpful for understanding the novel mechanisms of metastasis.

scholarly journals Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo

2020 ◽  
Vol 117 (37) ◽  
pp. 22910-22919
Author(s):  
Xingkang He ◽  
Xin Yin ◽  
Jing Wu ◽  
Stina L. Wickström ◽  
Yanhong Duo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Car T Cells ◽  
Human T Cell ◽  
Car T ◽  
Metastatic Cancer Cells

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.

Morphological Damage Induced in vivo by Lonidamine on Human Metastatic Cancer Cells

Oncology ◽  
1984 ◽  
Vol 41 (1) ◽  
pp. 94-103 ◽  
Author(s):  
C. De Martino ◽  
T. Battelli ◽  
R. Cavaliere ◽  
C. Gallo Curcio ◽  
M. Bellocci ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Metastatic Cancer ◽  
Metastatic Cancer Cells

scholarly journals Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing

2021 ◽  
Author(s):  
Kai Miao ◽  
Aiping Zhang ◽  
Fangyuan Shao ◽  
Lijian Wang ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Expression Patterns ◽  
Cell Lineage ◽  
Tumour Cells ◽  
Lineage Tracing

Abstract Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a CellTag system-based single-cell lineage tracing approach to show the metastasis rate and route of breast cancer cells and their interactions with the tumour microenvironment (TME) during metastasis. The results indicate that only a small fraction of cells can intravasate from the primary site into the blood circulation, whereas more cells disseminate through the lymphatic system to different organs. Tumour cells derived from the same progenitor cell exhibit different gene expression patterns in different soils, and the cancer cell-TME communication paradigm varies significantly between primary and metastatic tumours. Furthermore, metastable cells require a prewired IL-2 expression ability to migrate in vivo. In summary, leveraging a single-cell lineage tracing system, we demonstrate that the crosstalk between tumour cells and the TME is the driving force controlling the preferential metastatic fate of cancer cells through the lymphatic system and that this metastasis can be suppressed by knockdown of IL-2.

scholarly journals Functional single-cell profiling identifies that exosomes are associated with increased immune cell infiltration in non-metastatic breast cancer

2020 ◽  
Author(s):  
Mohsen Fathi ◽  
Robiya Joseph ◽  
Jay R T Adolacion ◽  
Melisa Martinez-Paniagua ◽  
Xingyue An ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Cell Lines ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Tumor Formation ◽  
In Vivo Studies ◽  
Metastatic Cells ◽  
Metastatic Cancer Cells

Exosomes mediate intercellular communication in health and disease. Conventional assays are limited in profiling exosomes secreted from large populations of cells and are unsuitable for studying the functional consequences of individual cells exhibiting varying propensity for exosome secretion. In cancer, since exosomes can support the development of the pre-metastatic niche, cells with varying abilities to secrete exosomes can directly impact tumorigenesis. Here, we developed a high throughput single-cell technique that enabled the mapping of exosome secretion dynamics. By utilizing clinically relevant models of breast cancer, we established that non-metastatic cancer cells secrete more exosomes than metastatic cancer cells. Single-cell RNA-sequencing confirmed that pathways related to exosome secretion were enriched in the non-metastatic cells compared to the metastatic cells. We established isogenic clonal cell lines from non-metastatic cells with differing propensities for exosome secretion and showed that exosome secretion is an inheritable property preserved during cell division. Combined in vitro and in vivo studies with these cell lines suggested that exosome secretion can impede tumor formation. In human non-metastatic breast tumors, tumors with higher secretion of exosomes have a better prognosis, higher immune cytolytic activity, and enrichment of pro-inflammatory macrophages compared to tumors with lower secretion of exosomes. Our single-cell methodology can become an essential tool that enables the direct integration of exosome secretion with multiple cellular functions.

scholarly journals Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment

2019 ◽  
Vol 179 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Radoslaw Bednarek ◽  
Anna Selmi ◽  
Dagmara Wojkowska ◽  
Kamil Karolczak ◽  
Marcin Popielarski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cell ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Cell Surface Expression ◽  
Microvascular Endothelial Cell

Abstract Purpose To examine the involvement of the F11R/JAM-A protein in breast cancer metastasis, we utilized the F11R/JAM-A antagonistic peptide 4D (P4D) in experiments of transendothelial migration (TEM) of breast cancer cells. Methods Experiments were conducted in the mouse 4T1 breast cancer model utilizing the human mammary epithelial cell and endothelial cell lines. The levels of soluble F11R/JAM-A (sJAM-A) in the murine plasmas were measured by ELISA. Levels of F11R/JAM-A mRNA and protein in cell lines were assessed by qRT-PCR and Western blot, respectively. Cell surface expression of F11R/JAM-A was demonstrated by flow cytometry. Functional tests included the TEM of breast cancer cells and adhesion of breast cancer cells to the endothelium. The endothelial permeability was studied by fluorescent tracer assay and by the Real-Time Cell Analysis (RTCA). Results The tumor inducers Tβ4 and TGF-β1 reduced the levels of sJAM-A in murine plasma, and reduced the F11R/JAM-A protein levels in the human microvascular endothelial cell line HMEC-1. The adhesion and TEM measured between breast cancer cells and inflamed or Tβ4-treated endothelium were inhibited by P4D. The presence of P4D did not destabilize the pre-existing tight junctions in the endothelial monolayer. The barrier-protecting effect of P4D was stronger than that of forskolin, when a booster dose of P4D was applied to the inflamed endothelium. Conclusions F11R/JAM-A protein can be considered as a novel target in the treatment of breast cancer metastasis. In vivo and clinical studies are needed to further investigate the effectiveness of F11R/JAM-A-derived peptide as a possible anti-metastatic drug.

scholarly journals Lévy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Sabil Huda ◽  
Bettina Weigelin ◽  
Katarina Wolf ◽  
Konstantin V. Tretiakov ◽  
Konstantin Polev ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Metastatic Cancer ◽  
Movement Patterns ◽  
Metastatic Cancer Cells

scholarly journals Chemotrap-1: An Engineered Soluble Receptor That Blocks Chemokine-Induced Migration of Metastatic Cancer Cells In vivo

2010 ◽  
Vol 70 (20) ◽  
pp. 8138-8148 ◽  
Author(s):  
Silvia Lanati ◽  
Darryl B. Dunn ◽  
Myriam Roussigné ◽  
Maxine S. Emmett ◽  
Virginie Carriere ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Metastatic Cancer ◽  
Soluble Receptor ◽  
Metastatic Cancer Cells

scholarly journals Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-An Chen ◽  
Yong-Da Sie ◽  
Tsung-Yun Liu ◽  
Hsiang-Ling Kuo ◽  
Pei-Yi Chou ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cancer Cells ◽  
Room Temperature ◽  
Metastatic Cancer ◽  
Normal Cells ◽  
Tgfβ Receptor ◽  
Membrane Type ◽  
Cell Invasiveness ◽  
And Control ◽  
Metastatic Cancer Cells

AbstractMetastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFβ receptor (TβRII), and TβRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TβRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TβRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness.

scholarly journals Amoebic Foraging Model of Metastatic Cancer Cells

Symmetry ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1140
Author(s):  
Daiki Andoh ◽  
Yukio-Pegio Gunji
Keyword(s):  
Bayesian Inference ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Gait Patterns ◽  
Lévy Walk ◽  
Levy Walk ◽  
Unicellular Organisms ◽  
Living Organisms ◽  
Walk Algorithm ◽  
Metastatic Cancer Cells

The Lévy walk is a pattern that is often seen in the movement of living organisms; it has both ballistic and random features and is a behavior that has been recognized in various animals and unicellular organisms, such as amoebae, in recent years. We proposed an amoeba locomotion model that implements Bayesian and inverse Bayesian inference as a Lévy walk algorithm that balances exploration and exploitation, and through a comparison with general random walks, we confirmed its effectiveness. While Bayesian inference is expressed only by P(h) = P(h|d), we introduce inverse Bayesian inference expressed as P(d|h) = P(d) in a symmetry fashion. That symmetry contributes to balancing contracting and expanding the probability space. Additionally, the conditions of various environments were set, and experimental results were obtained that corresponded to changes in gait patterns with respect to changes in the conditions of actual metastatic cancer cells.

scholarly journals Light- and Melanin Nanoparticle-Induced Cytotoxicity in Metastatic Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 965
Author(s):  
Victoria R. Gabriele ◽  
Robabeh M. Mazhabi ◽  
Natalie Alexander ◽  
Purna Mukherjee ◽  
Thomas N. Seyfried ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Metastatic Cancer ◽  
Energy Levels ◽  
Nanoparticle Concentration ◽  
Visible Radiation ◽  
Laser Illumination ◽  
Wide Range ◽  
Low Glucose ◽  
Melanin Nanoparticles ◽  
Metastatic Cancer Cells

Melanin nanoparticles are known to be biologically benign to human cells for a wide range of concentrations in a high glucose culture nutrition. Here, we show cytotoxic behavior at high nanoparticle and low glucose concentrations, as well as at low nanoparticle concentration under exposure to (nonionizing) visible radiation. To study these effects in detail, we developed highly monodispersed melanin nanoparticles (both uncoated and glucose-coated). In order to study the effect of significant cellular uptake of these nanoparticles, we employed three cancer cell lines: VM-M3, A375 (derived from melanoma), and HeLa, all known to exhibit strong macrophagic character, i.e., strong nanoparticle uptake through phagocytic ingestion. Our main observations are: (i) metastatic VM-M3 cancer cells massively ingest melanin nanoparticles (mNPs); (ii) the observed ingestion is enhanced by coating mNPs with glucose; (iii) after a certain level of mNP ingestion, the metastatic cancer cells studied here are observed to die—glucose coating appears to slow that process; (iv) cells that accumulate mNPs are much more susceptible to killing by laser illumination than cells that do not accumulate mNPs; and (v) non-metastatic VM-NM1 cancer cells also studied in this work do not ingest the mNPs, and remain unaffected after receiving identical optical energy levels and doses. Results of this study could lead to the development of a therapy for control of metastatic stages of cancer.

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