Validation of an in vitro model of erbB2+ cancer cell redirection

Park, Jang Pyo; Blanding, Walker M.; Feltracco, Jessica A.; Booth, Brian W.

doi:10.1007/s11626-015-9889-8

Cited by 10 publications

(18 citation statements)

References 44 publications

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“…These results suggest that cancer cells are responsive to external stimuli and can even be reverted back to the wild-type tissue phenotype by the signaling from cells within a healthy environment. This phenomenon has been termed "cancer cell redirection" [6].…”

Section: Introductionmentioning

confidence: 99%

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using in vivo and in vitro models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either in vivo or in vitro, they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.

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Section: Introductionmentioning

confidence: 99%

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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“…Not only are mouse tumor-derived cells susceptible to redirection [ 8 , 11 ] but human breast cancer and embryonic testicular carcinoma cells have been redirected [ 9 – 10 ]. Both human female and male derived cancer cells differentiated into functional breast epithelial cells in response to signals from the normal mouse mammary microenvironment [ 8 – 11 ]. This suggests that human cancers are reactive to controlling intercellular signals present in developing mammalian tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Establishment of the MMTV-neu cell lines is described elsewhere [ 11 ]. MMTV-neu cells were maintained in DMEM supplemented with 10% FBS and 1% antibiotic/antimycotic.…”

Section: Methodsmentioning

confidence: 99%

“…Successful redirection of human breast cancer cells and mouse mammary tumor cells occurs at a ratio of 1 cancer cell for every 50 normal epithelial cells while redirection of embryonal testicular carcinoma cells can occur at a ratio of 1 cancer cell for every 10 normal cells. When mouse mammary-tumor derived cells that overexpress erbB2 are redirected, the auto-phosphorylation of the erbB2 tyrosine kinase is attenuated while total expression of erbB2 is not impacted [ 11 ]. Reduced erbB2 phosphorylation is one mechanism involved in cancer cell redirection and detection of reduced receptor activity serves as a biomarker of cancer cell redirection.…”

Section: Introductionmentioning

confidence: 99%

“…We have developed an in vitro system of cancer cell redirection that employs the 1:50 ratio of erbB2-overexpressing cancer cells to normal cells [ 11 ]. This in vitro system has been validated as an alternative to the in vivo model.…”

Section: Introductionmentioning

confidence: 99%

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Cancer cell redirection biomarker discovery using a mutual information approach

et al. 2017

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Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.

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Characterization and Separation of Cancer Cells with a Wicking Fiber Device

2017

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Current cancer diagnostic methods lack the ability to quickly, simply, efficiently, and inexpensively screen cancer cells from a mixed population of cancer and normal cells. Methods based on biomarkers are unreliable due to complexity of cancer cells, plasticity of markers, and lack of common tumorigenic markers. Diagnostics are time intensive, require multiple tests, and provide limited information. In this study, we developed a novel wicking fiber device that separates cancer and normal cell types. To the best of our knowledge, no previous work has used vertical wicking of cells through fibers to identify and isolate cancer cells. The device separated mouse mammary tumor cells from a cellular mixture containing normal mouse mammary cells. Further investigation showed the device separated and isolated human cancer cells from a heterogeneous mixture of normal and cancerous human cells. We report a simple, inexpensive, and rapid technique that has potential to identify and isolate cancer cells from large volumes of liquid samples that can be translated to on-site clinic diagnosis.

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Validation of an in vitro model of erbB2+ cancer cell redirection

Cited by 10 publications

References 44 publications

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Cancer cell redirection biomarker discovery using a mutual information approach

Characterization and Separation of Cancer Cells with a Wicking Fiber Device

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