Heterogeneous Circulating Tumor Cells in Sarcoma: Implication for Clinical Practice

Agnoletto, Chiara; Caruso, Chiara; Garofalo, Cecilia

doi:10.3390/cancers13092189

Cited by 9 publications

(9 citation statements)

References 251 publications

(373 reference statements)

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“…Developmental biologists have defined EMT “as a phenotypic transformation linked with metastasis and a morphological conversion taking place at particular sites within embryonic epithelia to produce individual migratory cells” [27] . Comparable observations are also reported by cancer researchers [28] , [29] , [30] . Consequently, based on the biological context, EMT has now been classified into three types ( Fig.…”

Section: Types Of Emtsupporting

confidence: 86%

Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition

Saliem

Bede

Cooper

et al. 2022

Japanese Dental Science Review

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Section: Types Of Emtsupporting

confidence: 86%

Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition

Saliem

Bede

Cooper

et al. 2022

Japanese Dental Science Review

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“…Twenty-four hours after HCQ treatment (Figure 10A), the expression of E-cadherin mRNA in CIS-treated A549 cells was further reduced under hypoxic conditions (Figure 10B), suggesting acquisition of mesenchymal phenotype (EMT). As this phenotype is one of a characteristic of cancer stem cells (CSCs) (48,49), stemness-related markers were tested: OCT-3/4, NANOG, SOX2, and ALDH1. HCQ reduced expression of SOX-2 and NANOG in hypoxic CIS-treated cells both on mRNA (Supplementary Figures 8A, B) and protein level (Figures 10C-E).…”

Section: Autophagy Inhibition By Hcq Reduced Escape From Senescence Of Cis-treated Lung Cancer Cells Under Hypoxic Conditionsmentioning

confidence: 99%

Escape From Cisplatin-Induced Senescence of Hypoxic Lung Cancer Cells Can Be Overcome by Hydroxychloroquine

et al. 2022

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Chemotherapy is the commonly used treatment for advanced lung cancer. However, it produces side effects such as the development of chemoresistance. A possible responsible mechanism may be therapy-induced senescence (TIS). TIS cells display increased senescence-associated β-galactosidase (SA-β-gal) activity and irreversible growth arrest. However, recent data suggest that TIS cells can reactivate their proliferative potential and lead to cancer recurrence. Our previous study indicated that reactivation of proliferation by TIS cells might be related with autophagy modulation. However, exact relationship between both processes required further studies. Therefore, the aim of our study was to investigate the role of autophagy in the senescence-related chemoresistance of lung cancer cells. For this purpose, human and murine lung cancer cells were treated with two commonly used chemotherapeutics: cisplatin (CIS), which forms DNA adducts or docetaxel (DOC), a microtubule poison. Hypoxia, often overlooked in experimental settings, has been implicated as a mechanism responsible for a significant change in the response to treatment. Thus, cells were cultured under normoxic (~19% O2) or hypoxic (1% O2) conditions. Herein, we show that hypoxia increases resistance to CIS. Lung cancer cells cultured under hypoxic conditions escaped from CIS-induced senescence, displayed reduced SA-β-gal activity and a decreased percentage of cells in the G2/M phase of the cell cycle. In turn, hypoxia increased the proliferation of lung cancer cells and the proportion of cells proceeding to the G0/G1 phase. Further molecular analyses demonstrated that hypoxia inhibited the prosenescent p53/p21 signaling pathway and induced epithelial to mesenchymal transition in CIS-treated cancer cells. In cells treated with DOC, such effects were not observed. Of importance, pharmacological autophagy inhibitor, hydroxychloroquine (HCQ) was capable of overcoming short-term CIS-induced resistance of lung cancer cells in hypoxic conditions. Altogether, our data demonstrated that hypoxia favors cancer cell escape from CIS-induced senescence, what could be overcome by inhibition of autophagy with HCQ. Therefore, we propose that HCQ might be used to interfere with the ability of senescent cancer cells to repopulate following exposure to DNA-damaging agents. This effect, however, needs to be tested in a long-term perspective for preclinical and clinical applications.

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“…Thus, International consortia, including the European Liquid Biopsy Society, recommend that CTCs detection need more standardization. [114] Standardized assay protocols for sample preparation, handling, enrichment, detection, and evaluation are crucial to yield convincing and reproducible results, and ensure the generalized use of the approach. [98,115] Herein, we provide some opinions of how to establish the standards.…”

Section: Ctcs Detection Needs More Standardizationmentioning

confidence: 99%

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

Huang

Zhou

et al. 2022

Small Methods

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cells (CTCs) are precursors of metastasis in various cancers. They are detached cells slough off the edges of a solid tumor, and then enter the bloodstream or lymphatic system, moving from the primary site to distal organs via the lymphatic channels or the circulation. Although an estimated number of 3.2 × 10 6 tumor cells detach from one gram of tumor tissues per day, [2] CTCs have a relatively short life span that most of them begin to apoptosis within 24 h due to the loss of adhesion to the extracellular matrix, the shear forces of blood flow, or attacks from the immune cells. [3,4] Only a tiny fraction of CTCs that have undergone epithelial-mesenchymal transition (EMT) or CTC clusters formation survive in the bloodstream. [5] After EMT, epithelial CTCs acquire a mesenchymal phenotype, and become invasive and motile. CTCs hold the genetic information of the primary tumor, due to their same origin, thus can act as the surrogate of primary tumor for the monitoring of tumor phenotype/genotype. [6] CTCs counts have been reported correlate to overall survival and/or metastatic relapse, and suggested as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. [7] However, CTCs detection and analysis have two major challenges: their rarity in a typically sampled blood volume (10-50 mL), as well as genetical and phenotypical heterogeneity. [8] Thus, enrichment and detection procedures are the foundation for developing the technologies of CTCs detection. Microfluidic chip is a promising technology for CTCs isolation, identification, and characterization by using their biological and physical properties. It owes unique advantages, such as low-cost, simplicity, reduction in reagent consumption, miniaturization, fast and precise control.The substantial heterogeneity of CTCs determines their variability in expression patterns, [9] which causes difficulties to define a CTC by using specific markers. The most widely used markers to identify CTCs are EpCAM and cytokeratins (CKs). Thus, a long time in the early days, CTCs are defined as EpCAM or CKs positive and CD45 negative. But only epithelial CTCs express these two proteins. CTCs undergoing EMT gradually lose their epithelial features, having no or very low expression of epithelial markers (e.g., EpCAM, CKs, Circulating tumor cells (CTCs) enumeration has been widely used as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. Microfluidic technologies for CTCs enrichment and detection have been developed and commercialized as automation platforms. Currently, in addition to CTCs, some new types of circulating cancer-related cells (e.g., CCSCs, CTECs, CAMLs, and heterotypic CTC clusters) in circulation are also reported to be correlated to cancer diagnosis, metastasis, or prognosis. And they widely differ from the conventional CTCs in positive markers, cellular morphology, or size, which presents a new technological challenge to microfluidic devices that use ...

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Heterogeneous Circulating Tumor Cells in Sarcoma: Implication for Clinical Practice

Cited by 9 publications

References 251 publications

Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition

Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition

Escape From Cisplatin-Induced Senescence of Hypoxic Lung Cancer Cells Can Be Overcome by Hydroxychloroquine

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

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