The physics for the formation of cell-in-cell structures.

Ning, Xinjie; Luo, Tao; Chen, Z; Sun, Qiang

doi:10.2174/1566524015666151026105123

Cited by 21 publications

(19 citation statements)

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“…Whereas, heterogeneities within tumor clones drive CIC formation, the process has been shown to be complex and genetically controlled (19). E-cadherin-mediated adherens junctions bring cells together, and set up asymmetric RhoA activity to drive cell internalization (8,9) with the assistance of optimal membrane cholesterol and lipids (20) and the inflammatory cytokine IL-8 (21).…”

Section: Discussionmentioning

confidence: 99%

High Frequency of Cell-in-Cell Formation in Heterogeneous Human Breast Cancer Tissue in a Patient With Poor Prognosis: A Case Report and Literature Review

Ruan

Niu²,

Jiang

et al. 2019

Front. Oncol.

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Cell cannibalism is a unique pathological phenomenon that has been observed at low frequency in a variety of human tumor samples (<0.5%), including breast cancer. Cannibalistic cells typically form cell-in-cell (CIC) structures characterized by enclosure of one cell or more by another, mediating a novel type of cell death "entosis," which was proposed as the type IV cell death. A large number of CIC structures are generally associated with malignant transformation and progression, and they are believed to be primed by and form among heterogeneous cells. However, there is currently no in vivo evidence from human tumor samples. In this case report, covering a 37-year-old female breast cancer patient, we observed considerable heterogeneity and proliferative activity (>70% Ki-67 positivity) in her breast cancer cells, accompanied by high frequency of CIC formation (∼6%) and poor prognosis. We consider this a typical example of cell cannibalism, supporting a role of heterogeneity in cell-in-cell formation and malignant progression. It may serve as a pretest basis for further investigations of cell-in-cell biology and breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%

High Frequency of Cell-in-Cell Formation in Heterogeneous Human Breast Cancer Tissue in a Patient With Poor Prognosis: A Case Report and Literature Review

Ruan

Niu²,

Jiang

et al. 2019

Front. Oncol.

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“…In tumors, via internalizing and killing the less fit “loser” tumor cells, and endowing aneuploidy to the progenies of outer “winner” tumor cells ( 2 , 3 ), CIC formation could serve as a mechanism of cell competition to promote clonal selection and therefore tumor evolution ( 4 ). Based on recent research on entosis, a CIC-mediated nonapoptotic cell death process ( 5 ), the mechanisms underlying formation of homotypic CICs between cells of epithelial origin are starting to be revealed ( 6 ). Current research fits a working model of two core elements: first, adherens junction, mediated by epithelial complexes formed by E- or P-cadherin and multiple essential catenins ( 7 , 8 ), brings cells together and sets up asymmetric RhoA activity by junction localized-p190A RhoGAP.…”

Section: Introductionmentioning

confidence: 99%

“…Current research fits a working model of two core elements: first, adherens junction, mediated by epithelial complexes formed by E- or P-cadherin and multiple essential catenins ( 7 , 8 ), brings cells together and sets up asymmetric RhoA activity by junction localized-p190A RhoGAP. Then, activated RhoA/ROCKs signaling drives actomyosin contraction and the following cell internalization ( 6 ). Besides, glucose starvation and membrane cholesterol/lipids were found important regulators of entotic CIC formation probably by affecting the phosphorylation of myosin light chain (MLC) ( 9 , 10 ), suggesting CIC formation is a complex and finely controlled process.…”

Section: Introductionmentioning

confidence: 99%

Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation

Ruan

Wang

Chen³

et al. 2018

BMB Rep.

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Homotypic cell-in-cell (CIC) structures forming between cancer cells were proposed to promote tumor evolution via entosis, a nonapoptotic cell death process. However, the mechanisms underlying their formation remained poorly understood. We performed a microarray analysis to identify genes associated with homotypic CIC formation. Cancer cells differing in their ability to form homotypic CIC structures were selected for the study. Association analysis identified 73 probe sets for 62 candidate genes potentially involved in CIC formation. Among them, twenty-one genes were downregulated while 41 genes were upregulated. Pathway analysis identified a gene interaction network centered on IL-8, which was upregulated in high CIC cells. Remarkably, CIC formation was significantly inhibited by IL-8 knockdown and enhanced upon recombinant IL-8 treatment, which correlated with altered cell-cell adhesion and expression of adhesive molecules such as P-cadherin and γ-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion.

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“…Latest researches indicated that cell-in-cell formation by entosis is a key mechanism of cell competition to promote clonal selection and tumor evolution [42–44]. Despite being reported over a century, cell-in-cell remains largely mysterious in its forming mechanisms although progress were made recently [45–47]. Since blocking CD47 by antibodies could efficiently induce macrophage-mediated phagocytosis of tumor cells and treat cancers, it would be interesting to examine whether CD47 also participate in cell-in-cell formation between tumors, and if so, would blocking CD47 a feasible way to inhibit tumor growth by inducing cell-in-cell formation and the mediated-cell death?…”

Section: Discussionmentioning

confidence: 99%

A fully human anti-CD47 blocking antibody with therapeutic potential for cancer

et al. 2016

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CD47/SIRPα interaction serves as an immune checkpoint for macrophage-mediated phagocytosis. Mouse anti-CD47 blocking antibodies had demonstrated potent efficacy in the treatment of both leukemic and solid tumors in preclinical experimentations, and therefore had moved forward rapidly into clinical trials. However, a fully human blocking antibody, which meets clinical purpose better, has not been reported for CD47 up to date. In this study, we reported the isolation of a fully human anti-CD47 blocking antibody, ZF1, from a phage display library. ZF1 displayed high specificity and affinity for CD47 protein, which were comparable to those for humanized anti-CD47 blocking antibody B6H12. Importantly, ZF1 treatment could induce robust, or even stronger than B6H12, phagocytosis of leukemic cancer cells by macrophage in vitro, and protect BALB/c nude mice from cancer killing by engrafted leukemic cells (CCRF and U937) to a similar extent as B6H12 did. Thus, these data provide primary early pre-clinical support for the development of ZF1 as a fully human blocking antibody to treat human leukemia by targeting CD47 molecule.

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The physics for the formation of cell-in-cell structures.

Cited by 21 publications

References 0 publications

High Frequency of Cell-in-Cell Formation in Heterogeneous Human Breast Cancer Tissue in a Patient With Poor Prognosis: A Case Report and Literature Review

High Frequency of Cell-in-Cell Formation in Heterogeneous Human Breast Cancer Tissue in a Patient With Poor Prognosis: A Case Report and Literature Review

Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation

A fully human anti-CD47 blocking antibody with therapeutic potential for cancer

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