Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype

The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions.

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Abstract 397: Increased Rho GTPase and reduced glycolysis activity in metastatic cancer cells.

10.1158/1538-7445.am2013-397 ◽

2013 ◽

Author(s):

Pei-Fen Su ◽

Shu-Hao Chang ◽

Chia-Hsin Ho ◽

Wei-Li Huang

Keyword(s):

Cancer Cells ◽

Rho Gtpase ◽

Metastatic Cancer ◽

Metastatic Cancer Cells

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Preparation of a novel injectable in situ-gelling nanoparticle with applications in controlled protein release and cancer cell entrapment

RSC Advances ◽

10.1039/c8ra06589f ◽

2018 ◽

Vol 8 (60) ◽

pp. 34625-34633 ◽

Cited By ~ 5

Author(s):

Min Kyung Khang ◽

Jun Zhou ◽

Yihui Huang ◽

Amirhossein Hakamivala ◽

Liping Tang

Keyword(s):

Body Temperature ◽

Cancer Cells ◽

Cancer Cell ◽

Metastatic Cancer ◽

Protein Release ◽

Cell Entrapment ◽

In Situ Gelling ◽

Metastatic Cancer Cells

At body temperature, thermosensitive nanoparticles release erythropoietin to lure metastatic cancer cells.

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The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases

Cancers ◽

10.3390/cancers11071020 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1020 ◽

Cited By ~ 14

Author(s):

Alexus D. Kolb ◽

Karen M. Bussard

Keyword(s):

Extracellular Matrix ◽

Cancer Cells ◽

Bone Remodeling ◽

Cancer Cell ◽

Metastatic Cancer ◽

Bone Matrix ◽

Type I ◽

Bone Homeostasis ◽

Inorganic Components ◽

Metastatic Cancer Cells

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to maintain bone homeostasis and remodeling through cellular communication and response to biophysical signals from the ECM. However, under pathological conditions, including osteoporosis and cancer, bone remodeling is dysregulated. Once in the bone matrix, disseminated tumor cells utilize normal products of bone remodeling, such as collagen type I, to fuel cancer cell proliferation and lesion outgrowth. Models to study the complex interactions between the bone matrix and metastatic cancer cells are limited. Advances in understanding the interactions between the bone ECM and bone metastatic cancer cells are necessary in order to both regulate and prevent metastatic cancer cell growth in bone.

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Cancer cell fusion: a potential target to tackle drug-resistant and metastatic cancer cells

Drug Discovery Today ◽

10.1016/j.drudis.2019.05.024 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1836-1844 ◽

Cited By ~ 2

Author(s):

Clara Fernandes ◽

Priyanka Prabhu ◽

Kapil Juvale ◽

Divya Suares ◽

Mayur YC

Keyword(s):

Cancer Cells ◽

Cell Fusion ◽

Cancer Cell ◽

Metastatic Cancer ◽

Drug Resistant ◽

Potential Target ◽

Metastatic Cancer Cells

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

Communications Biology ◽

10.1038/s42003-021-02271-2 ◽

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.

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Amoebic Foraging Model of Metastatic Cancer Cells

Symmetry ◽

10.3390/sym13071140 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13070965 ◽

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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The In Vivo Selection Method in Breast Cancer Metastasis

International Journal of Molecular Sciences ◽

10.3390/ijms22041886 ◽

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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