scholarly journals Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas E. Stone ◽  
Abhishek Raj ◽  
Katherine M. Young ◽  
Adam P. DeLuca ◽  
Fatima Ezahra Chrit ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Personalized Medicine ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cell Sorting ◽  
Metastatic Cancer ◽  
Patient Specific ◽  
Surface Markers ◽  
Label Free ◽  
Metastatic Cancer Cells

AbstractThe isolation of a patient's metastatic cancer cells is the first, enabling step toward treatment of that patient using modern personalized medicine techniques. Whereas traditional standard-of-care approaches select treatments for cancer patients based on the histological classification of cancerous tissue at the time of diagnosis, personalized medicine techniques leverage molecular and functional analysis of a patient's own cancer cells to select treatments with the highest likelihood of being effective. Unfortunately, the pure populations of cancer cells required for these analyses can be difficult to acquire, given that metastatic cancer cells typically reside in fluid containing many different cell populations. Detection and analyses of cancer cells therefore require separation from these contaminating cells. Conventional cell sorting approaches such as Fluorescence Activated Cell Sorting or Magnetic Activated Cell Sorting rely on the presence of distinct surface markers on cells of interest which may not be known nor exist for cancer applications. In this work, we present a microfluidic platform capable of label-free enrichment of tumor cells from the ascites fluid of ovarian cancer patients. This approach sorts cells based on differences in biomechanical properties, and therefore does not require any labeling or other pre-sort interference with the cells. The method is also useful in the cases when specific surface markers do not exist for cells of interest. In model ovarian cancer cell lines, the method was used to separate invasive subtypes from less invasive subtypes with an enrichment of ~ sixfold. In ascites specimens from ovarian cancer patients, we found the enrichment protocol resulted in an improved purity of P53 mutant cells indicative of the presence of ovarian cancer cells. We believe that this technology could enable the application of personalized medicine based on analysis of liquid biopsy patient specimens, such as ascites from ovarian cancer patients, for quick evaluation of metastatic disease progression and determination of patient-specific treatment.

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.

scholarly journals Detection and Characterization of Metastatic Cancer Cells in the Mesogastrium of Gastric Cancer Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142970 ◽  
Author(s):  
Daxing Xie ◽  
Liang Liu ◽  
Hasan Osaiweran ◽  
Chaoran Yu ◽  
Fang Sheng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Gastric Cancer Patients ◽  
Metastatic Cancer Cells

scholarly journals Detection of metastatic cancer cells in mesentery of colorectal cancer patients

2017 ◽  
Vol 23 (34) ◽  
pp. 6315 ◽  
Author(s):  
Xue-Lai Luo ◽  
Da-Xing Xie ◽  
Jian-Xin Wu ◽  
An-Ding Wu ◽  
Zong-Qing Ge ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Colorectal Cancer Patients ◽  
Metastatic Cancer Cells

Activated coagulation factors in human malignant effusions and their contribution to cancer cell metastasis and therapy

2007 ◽  
Vol 97 (06) ◽  
pp. 1023-1030 ◽  
Author(s):  
Inke Lühr ◽  
Thomas Kunze ◽  
Christoph Mundhenke ◽  
Nicolai Maass ◽  
Tobias Erhart ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Coagulation System ◽  
Blood Coagulation Disorders ◽  
Thrombin Activation ◽  
Malignant Effusions ◽  
Metastatic Cancer Cells

SummaryWe have shown that the thrombin G-protein coupled receptors (GPCR) designated as protease-activated receptors (PAR-1) are expressed in primary cancer cells isolated from peritoneal and pleural malignant effusions. Here, our main goal was to evaluate several coagulation and thrombin activation effectors and markers in a series of 136 malignant effusions from cancer patients with gastrointestinal, lung and mammary carcinomas. All these patients present a highly activated coagulation system in blood and their malignant effusions, as indicated by high levels of prothrombin F1.2 fragments and D-dimers. Notably, we detected in the effusions all the coagulation factors of the tissue factor pathway inducing thrombin activation, namely factorsVII, V, X and II, as well as high VEGF levels and IGF-II in mature and precursor forms. Fibrin clot formation also correlated with higher levels of free ionized calcium (iCa), suggesting that iCa and its binding protein albumin are regulatory factors for fibrinogenesis in effusions. Consequently, thrombin,VEGF and IGFII appear to converge in the promotion of survival and invasivity of the metastatic cancer cells from blood to the malignant effusions. Thus, we add new insights on the interconnections between blood coagulation disorders in cancer patients and thrombin activation in malignant effusions, including their functional interaction with PAR in metastatic cancer cells. Based on these data we propose to counteract the metastatic cascades by targeted invalidation of key effectors of the coagulation system. Therefore, potential therapeutic approaches include the application of thrombin protease inhibitors, VEGF-blocking antibodies, and drugs targeting the VEGF and thrombin signaling pathways, such as tyrosine kinase or GPCR inhibitors.

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.

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.

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