Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy

Gong, Chang; Liu, Bodu; Yao, Yihong; Qu, Su; Luo, Wei; Tan, Weige; Liu, Qiang; Yao, Herui; Zou, Lee; Su, Fengxi; Song, Erwei

doi:10.1074/jbc.m115.652628

Cited by 36 publications

(40 citation statements)

References 46 publications

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“…Enhanced DNA repair capabilities were reported previously in CTCs from breast cancer compared to primary tumors. This finding is important and has clinical implications, especially when treating cancer patients with DNA-damaging therapies, such as anthracyclines and platinums, which are known DNA-damaging drugs that are routinely used for breast cancer treatment (57).…”

Section: Discussionmentioning

confidence: 99%

Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

Mohammed

et al. 2018

Preprint

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The molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. We developed an innovative technique that enables the collection of lymph and lymph-circulating tumor cells (LCTCs) en route to the SLN in immunocompetent animal model of breast cancer metastasis. We found that LCTCs and blood circulating tumor cells (BCTCs) as exited the primary tumor shared similar gene and protein expression profiles that were distinct from those of primary tumors and lymph node metastases (LNMs) despite their common parental cell origin. LCTCs but not BCTC exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell-like properties and constitute extraordinarily efficient metastatic precursors. These results demonstrate that tumor cell metastasizing through the lymphatic are different from those spread by the blood circulation. The contribution of these cells to overall peripheral blood CTC is important in cancer therapy. Whether these two types of cells occur in cancer patients remain to be determined.

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Section: Discussionmentioning

confidence: 99%

Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

Mohammed

et al. 2018

Preprint

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“…Isolation of CTCs. Isolation of human CTCs was performed as previously reported by Gong et al (28). Briefly, 20-50 ml fresh blood was obtained from lung adenocarcinoma patients and layered over Ficoll-Paque at a density of 1.077 g, and centrifuged at 400 x g for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

miR‑10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway

et al. 2020

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Circulating tumor cells (CTCs) that are shed from the primary tumor invade the blood stream or surrounding parenchyma to form new tumors. The present study aimed to explore the underlying mechanism of cisplatin resistance in lung adenocarcinoma CTCs and provide clinical treatment guidance for lung cancer treatment. CTCs from the blood samples of 6 lung adenocarcinoma patients were treated with different concentrations of cisplatin along with A549 and H1299 cells. The sensitivity of CTCs to cisplatin was explored by detecting the inhibitory rate via CCK-8 assay. The related molecular mechanism was investigated by western blot analysis. miR-10a expression was detected using quantitative real-time PCR (RT-qPCR). The relationship between miR-10a and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) was verified and further confirmed by luciferase reporter assay, western blotting and RT-qPCR assay. The results revealed that CTCs exhibited lower cisplatin sensitivity than A549 and H1299 cells. Moreover, CTCs treated with cisplatin demonstrated higher miR-10a expression and lower PIK3CA expression than that in A549 and H1299 cells (P<0.01). Expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation were also decreased in A549 and H1299 cells compared with CTCs after cisplatin treatment. PIK3CA is a target of miR-10a, and both miR-10a overexpression and PIK3CA knockdown obviously decreased the sensitivity of A549 and H1299 cells to cisplatin as well as the expression of PI3K and phosphorylation of Akt. PIK3CA overexpression attenuated the cisplatin resistance of A549 and H1299 cells induced by miR-10a. In conclusion, miR-10a suppressed the PI3K/Akt pathway to strengthen the resistance of CTCs to cisplatin via targeting PIK3CA, providing a new therapeutic target for lung cancer treatment.

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“…EMT downregulates the surface markers of epithelial cells and upregulates the markers of mesothelial cells, and then promotes tumor cells to break away from intercellular adhesion and acquire variability and invasiveness. MET enables CTCs with EMT to reverse and restore the epithelial phenotype, regain the ability of adhesion, and form metastases [16]. Because CTCs shed from solid tumor, they have the properties of epithelial cell and mesenchymal cell, and can express EpCAM antigen on their surface, which can be used to distinguish CTCs from blood cells.…”

Section: The Ctc Biological Properties For Isolationmentioning

confidence: 99%

Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis

Jiang

Wang

et al. 2020

Electrophoresis

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Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasisThe prognosis of malignant tumors is challenged by insufficient means to effectively detect tumors at early stage. Liquid biopsy using circulating tumor cells (CTCs) as biomarkers demonstrates a promising solution to tackle the challenge, because CTCs play a critical role in cancer metastatic process via intravasation, circulation, extravasation, and formation of secondary tumor. However, the effectiveness of the solution is compromised by rarity, heterogeneity, and vulnerability associated with CTCs. Among a plethora of novel approaches for CTC isolation and enrichment, microfluidics leads to isolation and detection of CTCs in a cost-effective and operation-friendly way. Development of microfluidics also makes it feasible to model the cancer metastasis in vitro using a microfluidic system to mimick the in vivo microenvironment, thereby enabling analysis and monitor of tumor metastasis. This paper aims to review the latest advances for exploring the dual-roles microfluidics has played in early cancer diagnosis via CTC isolation and investigating the role of CTCs in cancer metastasis; the merits and drawbacks for dominating microfluidics-based CTC isolation methods are discussed; biomimicking cancer metastasis using microfluidics are presented with example applications on modelling of tumor microenvironment, tumor cell dissemination, tumor migration, and tumor angiogenesis. The future perspectives and challenges are discussed.

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Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy

Cited by 36 publications

References 46 publications

Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

miR‑10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway

Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis

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