Antimetastatic Effect by Targeting CTC Cluster—Response

Choi, Jin Woo; Yoon, Kwon‐Ha; Yun, Seok Hyun

doi:10.1158/0008-5472.can-16-0974

Cited by 5 publications

(4 citation statements)

References 4 publications

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“…Application of the uPA inhibitor for a SCLC model employing human H510 cells, dose-dependently and signi cantly reduced primary tumor growth and numbers of lung metastases [73]. However, the breakdown of CTC clusters by uPA was shown to impair metastasis and reduction of secondary lesions [74][75][76]. Therefore, the CTC cluster-dissociating activity of uPA may outweigh its disease-driving effect under speci c conditions.…”

Section: Discussionmentioning

confidence: 99%

Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation

Rath

Plangger

Klameth

et al. 2022

Preprint

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Introduction: Coagulation is frequently activated in cancer patients and has been correlated with an unfavorable prognosis. To evaluate whether a release of tissue factor (TF) of circulating tumor cells (CTCs) is involved in the dissemination of small cell lung cancer (SCLC) we studied the expression of relevant proteins in a panel of permanent SCLC and SCLC CTC cell lines (BHGc7, BHGc10, BHGc16, BHGc26 and UHGc5) that have been established at our institution. Material and Methods Five CTC and SCLC lines were analyzed using Western blot arrays covering 55 angiogenetic mediators. Furthermore, the influence of topotecan and epirubicin as well as hypoxia-like conditions on the expression of these mediators and cells was investigated. Results The results demonstrate that the SCLC lines express no significant amounts of the TF but thrombospondin-1 (TSP-1), uPAR, VEGF and angiopoietin-2 in two cases. The major difference between the SCLC and SCLC CTC cell lines found was the loss of the expression of angiogenin in the blood-derived CTC lines. Topotecan and epirubicin decreased expression of VEGF, whereas hypoxia-like conditions upregulated VEGF. Conclusions Active TF seems not to be expressed in SCLC and SCLC CTC cell lines in significant levels and, thus, CTC-derived TF seems dispensable for dissemination. Nevertheless, all CTC lines form large spheroids, termed tumorospheres, which may become trapped in clots of the microvasculature and extravasate in this supportive microenvironment. The contribution of clotting to protection and dissemination of CTCs in SCLC seems to be different from other solid tumors such as breast cancer.

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Section: Discussionmentioning

confidence: 99%

Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation

Rath

Plangger

Klameth

et al. 2022

Preprint

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“…Circulating tumor cell (CTC) clusters (composed of two or more tumor cells) have a metastatic advantage over individual CTCs [ 2 , 3 ], which makes them a very clinically relevant population of cells to be targeted. Targeting CTC clusters is considered to be an effective therapeutic strategy [ 4 , 5 ]. However, the underlying mechanisms of the high metastatic capacity of CTC clusters remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Systematic optimization and evaluation of culture conditions for the construction of circulating tumor cell clusters using breast cancer cell lines

Zou,

Chen,

et al. 2024

BMC Cancer

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Background Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

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“…Circulating tumor cell (CTC) clusters (composed of two or more tumor cells) have a metastatic advantage over individual CTCs [2][3], which makes them a very clinically relevant population of cells to target. Targeting CTC clusters is considered to be an effective therapeutic strategy [4][5], however, the underlying mechanisms of the high metastatic capacity of CTC clusters remain to be investigated. The rare number of CTC clusters and the difficulty of capturing them have prevented researchers from obtaining sufficient numbers of CTC clusters for downstream analysis [4], resulting in a very slow development of the molecular biology of CTC clusters.…”

Section: Introductionmentioning

confidence: 99%

Systematic optimization of culture conditions and evaluation of in vitro Circulating tumor cell clusters

Chen

Zou

Chen

et al. 2023

Preprint

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Circulating tumor cell (CTC) clusters runs a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have blocked research progress. In vitro CTC clusters model can help us further understand the biological properties of CTC clusters and their clinical significance. It is worth noting that the biological variability of in vitro CTC clusters model due to different culture conditions has a non-negligible impact on the experimental results. Therefore, it is necessary to examine the biological similarity of in vitro CTC cluster models with clinical CTC clusters. Here, we optimized the culture method for the in vitro CTC cluster model based on the physiological environment of CTC in the circulatory system, and more importantly, we emphasized the importance of evaluating the in vitro CTC cluster models with reference to the biological characteristics of reported real CTC clusters, and assessed the similarity of the in vitro CTC clusters model, providing a reliable method for the study of CTC clusters.

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Antimetastatic Effect by Targeting CTC Cluster—Response

Cited by 5 publications

References 4 publications

Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation

Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation

Systematic optimization and evaluation of culture conditions for the construction of circulating tumor cell clusters using breast cancer cell lines

Systematic optimization of culture conditions and evaluation of in vitro Circulating tumor cell clusters

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