Survival Mechanisms and Influence Factors of Circulating Tumor Cells

Wang, Wenchao; Peng, Jian; Li, Xifeng; Wang, Aili; Bie, Ya-Qin; Shi, Liangrong; Lin, Moubin; Zhang, Xiaofeng

doi:10.1155/2018/6304701

Cited by 82 publications

(67 citation statements)

References 57 publications

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“…Single-cell sequencing data have shown increased expression of the EMT and stemness markers in CTCs (12). It has been postulated that activation of the EMT program facilitates CTC generation and enhances cancer cell survival in the circulation system (7,51). We found that Twist-induced EMT significantly enhanced MEC-platelet interaction, platelet-dependent extravasation, and MEC retention in the lung.…”

Section: Discussionmentioning

confidence: 64%

Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction

Xiong

Chen

Zhang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretion and deposition, were highly expressed during the epithelial-mesenchymal transition (EMT) and in CTCs. Hsp47 expression induced mesenchymal phenotypes in mammary epithelial cells (MECs), enhanced platelet recruitment, and promoted lung retention and colonization of cancer cells. Platelet depletion in vivo abolished Hsp47-induced cancer cell retention in the lung, suggesting that Hsp47 promotes cancer cell colonization by enhancing cancer cell–platelet interaction. Using rescue experiments and functional blocking antibodies, we identified type I collagen as the key mediator of Hsp47-induced cancer cell–platelet interaction. We also found that Hsp47-dependent collagen deposition and platelet recruitment facilitated cancer cell clustering and extravasation in vitro. By analyzing DNA/RNA sequencing data generated from human breast cancer tissues, we showed that gene amplification and increased expression of Hsp47 were associated with cancer metastasis. These results suggest that targeting the Hsp47/collagen axis is a promising strategy to block cancer cell–platelet interaction and cancer colonization in secondary organs.

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Section: Discussionmentioning

confidence: 64%

Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction

Xiong

Chen

Zhang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…One reason for this may be that the epithelial cancer cells use stromal cells during invasion [87,88] (see more detail below). Solid tumors secrete a large number of highly heterogeneous circulating tumor cells (CTCs) into the bloodstream [89][90][91][92][93][94][95]. Still, only a small proportion of the CTCs (0.2% reported by Tripathi et al [96]) can survive and ultimately result in metastatic changes.…”

Section: Circulating Cancer Cells Form Clusters Through Tomo-and Hetementioning

confidence: 99%

“…Approximately only one cell per 10 6 -10 7 leukocytes remain [94]. The molecular mechanisms responsible for the formation and spread of clusters, and the pathways supporting their survival and metastatic potential remain mostly unknown [93].…”

Section: Circulating Cancer Cells Form Clusters Through Tomo-and Hetementioning

confidence: 99%

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Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Alekseenko

Чернов

Kostrov

2020

Cancers

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The failure of therapies directed at targets within cancer cells highlight the necessity for a paradigm change in cancer therapy. The attention of researchers has shifted towards the disruption of cancer cell interactions with the tumor microenvironment. A typical example of such a disruption is the immune checkpoint cancer therapy that disrupts interactions between the immune and the cancer cells. The interaction of cancer antigens with T cells occurs in the immunological synapses. This is characterized by several special features, i.e., the proximity of the immune cells and their target cells, strong intercellular adhesion, and secretion of signaling cytokines into the intercellular cleft. Earlier, we hypothesized that the cancer-associated fibroblasts interacting with cancer cells through a synapse-like adhesion might play an important role in cancer tumors. Studies of the interactions between cancer cells and cancer-associated fibroblasts showed that their clusterization on the membrane surface determined their strength and specificity. The hundreds of interacting pairs are involved in the binding that may indicate the formation of synapse-like structures. These interactions may be responsible for successful metastasis of cancer cells, and their identification and disruption may open new therapeutic possibilities.

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“…It has also been observed that platelet interaction plays an important role in CTC survival. EMT-mediated platelet coating around the CTC surface provides a shield from natural killer (NK)-mediated tumor attack as well from the shear and dynamic stress in the bloodstream [46,47]. Furthermore, platelet depletion enhances the efficacy of NK cytolysis of CTCs [48].…”

Section: Ctcs In Circulationmentioning

confidence: 99%

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Huong

Gurshaney

Bình

et al. 2020

Cancers

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With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

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Survival Mechanisms and Influence Factors of Circulating Tumor Cells

Cited by 82 publications

References 57 publications

Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction

Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Emerging Role of Circulating Tumor Cells in Gastric Cancer

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