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, Banzhan; Niu, Zubiao; Jiang, Xiaoyi; Li, Zhuo; Tai, Yoshiaki; Huang, Hongyan; Sun, Qiang

doi:10.3389/fonc.2019.01444

Cited by 29 publications

(25 citation statements)

References 26 publications

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“…Further development of the model could allow for more variety in choosing the cell size, as well as for introducing additional cell lines to a heterogeneous tumor. Empirical data confirm that heterogeneous tumors indeed consist of various cells (Al-Brahim & Salama, 2005;Gerlinger et al, 2012;Stanta & Bonin, 2018), and that the cell size is important in cancer growth and propagation (Grichnik et al, 2006;Rosai, 2011;Lyons et al, 2016). Our model can help to explain that the cell size, in addition to other e.g., mechanical parameters (Sarna et al, 2018), may give the answer.…”

Section: Opportunitiessupporting

confidence: 60%

“…One of the simplest distinguishing features of a cell is its size. It is a well-known fact that the growth and the propagation of cancer vary depending on the cell size (Li & Lowengrub, 2014;Li et al, 2015;Schmoller, 2017), and that the size of the cells in a heterogeneous tumor differs (Sastre-Garau et al, 2004;Ruan et al, 2019;Xu et al, 2020). Therefore indeed, the cell size may be a good starting point for analyzing the cell population heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

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Growth of mixed cancer cell population – in silico the size matters

Kłos

Płonka

2020

Acta Biochim Pol

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Cancer heterogeneity is still underexplored and difficult to investigate. The whole network of factors engaged in tumor growth makes clinical cases, as well as the in vivo and in vitro experiments of limited use in terms of understanding cancer heterogeneity. Our idea was to start from scratch and focus on the simplest distinctive feature in a heterogeneous tumor, namely the cell size. To exclude any other factors, we created a rudimentary cellular automata model of mixed cancer culture with two lines of different cell sizes. We tested the model with various sets of parameters to explore how the cell size affects cancer co-culture growth. It turned out that the cell size plays a crucial role in in silico heterogeneous tumor growth. The dominance of bigger cells decreases the number of cells in the overall mixed cancer population. In contrast, the small cells increase the total number of cells, even without a parallel enlargement of the macroscopic tumor size. The predominance of the smaller cells is particularly visible in overcrowded conditions. Although our model was primarily designed for verification of experimental hypothesis and as a mean for better understanding of the cancer heterogeneity itself, it is as well of some practical value. Our findings can affect today’s practice of estimating tumor growth based on its macroscopic size and may propose a new approach to interpreting histological data. After modifications, the model may serve to test other factors affecting the growth of mixed populations of cancer cells differing in size.

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Section: Opportunitiessupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Growth of mixed cancer cell population – in silico the size matters

Kłos

Płonka

2020

Acta Biochim Pol

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“…One study revealed the poor outcome and disease recurrence of lung adenocarcinomas, associated with an increased number of entotic structures [ 28 ]. In the case report of one patient with invasive ductal carcinoma, a high frequency of entotic figures was accompanied by poor prognosis [ 30 ].…”

Section: Entosis In Cancermentioning

confidence: 99%

Entosis: From Cell Biology to Clinical Cancer Pathology

Młynarczuk-Biały

Dziuba²,

Sarnecka

et al. 2020

Cancers

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Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.

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“…Cell-in-cell (CIC) is an evolutionarily conserved cytobiological phenomenon ( 1 , 2 ), which was first reported 150 years ago by a German scholar ( 3 ). It refers to the presence of one or more living cells within another living one and has ever since been found in varieties of tumors tissues, such as breast carcinoma ( 4 , 5 ), pancreatic ductal adenocarcinoma ( 6 ), and head and neck squamous cell carcinoma (HNSCC) ( 7 ) and the like. CIC has two typical forms: one is homotypic CIC, and the other is heterotypic CIC, with the latter often occurring between tumor cells and immune cells that include neutrophils ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

et al. 2020

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Objective: To analyze the role of frequency of heterotypic neutrophil-in-tumor structure (FNiT) in the prognosis of patients with buccal mucosa squamous cell carcinoma (BMSCC). Methods: In vitro, we cocultured BMSCC cell line-H157 with neutrophils to form heterotypic neutrophil-in-tumor structures, which were then subject to fluorescence staining. Clinically, 145 patients were retrospectively enrolled. Associations between FNiT and clinicopathological variables including age, sex, smoking history, drinking history, betel nut chewing, tumor stage, node stage, metastasis, disease stage, lymphovascular invasion, extranodal extension, perineural invasion, and tumor grade were analyzed by chi-square test, and the main endpoints of interest were recurrence-free survival (RFS) and disease-specific survival (DSS) which were analyzed by the Kaplan-Meier method and Cox model. Results: Fluorescent staining results of typical heterotypic neutrophil-in-tumor structure showed that well-differentiated H157 cells had a stronger ability to internalize more neutrophils than poorly-differentiated H157 cells, with the latter often internalizing only one neutrophil or nothing. The mean FNiT was 4.2‰, with a range from 2.3‰ to 7.8‰. A total of 80 patients relapsed and 84 patients died of the disease. The 5-year RFS and DSS rate was 42% and 42%, respectively. Patients with an FNiT≥4.2‰ had a significantly higher risk for locoregional recurrence and cancer-caused death than those with an FNiT<4.2‰ (p=0.001 and p<0.001, respectively). The FNiT alone was independently significant in predicting poor RFS, and the FNiT along with tumor grade was an independent predictor for DSS. Conclusion: The FNiT as a novel predictor is significantly negatively associated with both the RFS and DSS of patients with BMSCC.

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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

Cited by 29 publications

References 26 publications

Growth of mixed cancer cell population – in silico the size matters

Growth of mixed cancer cell population – in silico the size matters

Entosis: From Cell Biology to Clinical Cancer Pathology

Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

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