The Complexities of Metastasis

Juan, Beatriz P. San; Garcia‐Leon, Maria Jesus; Rangel, Laura; Goetz, Jacky G.; Chaffer, Christine L.

doi:10.3390/cancers11101575

Cited by 32 publications

(29 citation statements)

References 194 publications

(236 reference statements)

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“…Its knockdown abrogates CTC cluster and suppresses lung metastasis in vivo . Consistently, in breast cancer patients, the abundance of CTC clusters and plakoglobin shows adverse outcomes, suggesting a clinical validation of observations in mouse models [ 135 ]. Similarly, p120-catenin which can stabilize E-cadherin levels by regulating its adhesive binding strength at the cell surface, could also be involved in regulating collective cell migration [ 136 ].…”

Section: Role Of Partial Emt In Collective Migrationmentioning

confidence: 78%

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Saxena

Jolly

Balamurugan

2020

Translational Oncology

141

112

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Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

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Section: Role Of Partial Emt In Collective Migrationmentioning

confidence: 78%

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Saxena

Jolly

Balamurugan

2020

Translational Oncology

141

112

View full text Add to dashboard Cite

show abstract

“…2 a–c). Since colon cancer liver metastasis is one of the main obstacles in colon cancer treatment [ 13 ]. We next assessed the effects of CNT-CpG on metastasis of colon cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…Epithelial–mesenchymal transition (EMT) is the major cellular event carried out during both tumorigenesis and metastasis [ 13 ]. EMT is feathered by losing cell junctions, epithelial characteristics and cell polarity progress contributing to tumor metastasis and invasiveness [ 13 , 14 ]. Moreover, cancer cells that have undergone EMT are more malignant, displaying increased cancer feathers [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells

Jin¹,

Gao

Song³

et al. 2020

Anti-Cancer Drugs

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Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and suppress the colon cancer liver metastasis has not been evaluated. In this study, we report CNT enhances CpG uptake in mouse colon cancer cells. Results demonstrated only CpG with CNT conjugation showed significant activation of NF-κB signal. Moreover, intratumorally delivery of CNT-CpG successfully suppressed local xenograft tumor growth and liver metastasis. CNT-CpG treatments cured 75% of mice and inhibited local tumor growth, significantly prolonged survival outcomes and limited liver metastatic tumor nodules from colon cancer cells. Using human colon cancer cell line, HCT116, we observed significantly inhibitory effects of CNT-CpG on cell growth, invasion and migration. Importantly, CNT-CpG treatment blocked the epithelial to mesenchymal transition (EMT). We compared the mRNA levels of EMT markers of colon cancer cells without or with CNT-CpG treatment from in-vitro and in-vivo models. Consistent results demonstrated expression of epithelial marker, E-cadherin was upregulated by CNT-CpG. In contrast, three mesenchymal markers, snail, fibronectin and vimentin were significantly suppressed by CNT-CpG treatment compared with control or free CpG. In summary, our data suggest CNT-CpG is an effective therapeutic approach against local colon tumor and their liver metastasis. This study presents the CNT-CpG complex as a promising therapeutic target for developing novel therapies against both local colon tumors and liver metastatic tumors.

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“…Formation of metastatic sites relies on adhesion of CTCs to the endothelial cells. This process depends not only on the adhesion receptors of CTCs but also on the receptor repertoire of accompanying cells or fractions such as neutrophils and platelets [ 50 ]. As soon as the CTCs adhere to the endothelia in the target organs, recruitment of platelet and granulocytes promotes the early metastatic niches.…”

Section: Interaction Of Ctc and Metastatic Nichementioning

confidence: 99%

Critical steps to tumor metastasis: alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche

Zhuyan

Chen

Zhu³

et al. 2020

Cell Biosci

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For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that premetastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells' infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the "Seed and Soil" hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.

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The Complexities of Metastasis

Cited by 32 publications

References 194 publications

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells

Critical steps to tumor metastasis: alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche

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