Tetraspanins: Novel Molecular Regulators of Gastric Cancer

Deng, Yue; Cai, Sicheng; Shen, Jian; Peng, Hongxia

doi:10.3389/fonc.2021.702510

Cited by 30 publications

(28 citation statements)

References 99 publications

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“…The expression of CD9 is diminished in gastric cancer and has been proposed to be inversely associated with lymph node metastasis and with increased recurrence risk [ 39 , 40 , 41 ]. These findings would concur with our results showing that the lack of CD9 expression on exosomes produced by CRC cells enhanced their interaction and uptake by recipient cells.…”

Section: Discussionmentioning

confidence: 99%

Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells

Cardeñes

Clares

Toribio

et al. 2021

IJMS

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Approximately 25% of colorectal cancer (CRC) patients develop peritoneal metastasis, a condition associated with a bleak prognosis. The CRC peritoneal dissemination cascade involves the shedding of cancer cells from the primary tumor, their transport through the peritoneal cavity, their adhesion to the peritoneal mesothelial cells (PMCs) that line all peritoneal organs, and invasion of cancer cells through this mesothelial cell barrier and underlying stroma to establish new metastatic foci. Exosomes produced by cancer cells have been shown to influence many processes related to cancer progression and metastasis. In epithelial ovarian cancer these extracellular vesicles (EVs) have been shown to favor different steps of the peritoneal dissemination cascade by changing the functional phenotype of cancer cells and PMCs. Little is currently known, however, about the roles played by exosomes in the pathogenesis and peritoneal metastasis cascade of CRC and especially about the molecules that mediate their interaction and uptake by target PMCs and tumor cells. We isolated exosomes by size−exclusion chromatography from CRC cells and performed cell-adhesion assays to immobilized exosomes in the presence of blocking antibodies against surface proteins and measured the uptake of fluorescently-labelled exosomes. We report here that the interaction between integrin α5β1 on CRC cells (and PMCs) and its ligand ADAM17 on exosomes mediated the binding and uptake of CRC-derived exosomes. Furthermore, this process was negatively regulated by the expression of tetraspanin CD9 on exosomes.

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Section: Discussionmentioning

confidence: 99%

Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells

Cardeñes

Clares

Toribio

et al. 2021

IJMS

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“…Tetraspanins are multifunctional transmembrane proteins involved, among others, in the regulation of adhesion, integrin signaling, metalloproteinase activity and antigen presentation. They can also act as tumor suppressors or oncogenic proteins by regulating proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) [ 58 , 59 , 60 , 61 , 62 ]. It is worth noting, however, that many tetraspanins have different functions depending on the type of cancer.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?

Grzanka

Stachurska-Skrodzka

Adamiok‐Ostrowska

et al. 2022

IJMS

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Extracellular vesicles (EVs) are small, membranous structures involved in intercellular communication. Here, we analyzed the effects of thyroid cancer-derived EVs on the properties of normal thyroid cells and cells contributing to the tumor microenvironment. EVs isolated from thyroid cancer cell lines (CGTH, FTC-133, 8505c, TPC-1 and BcPAP) were used for treatment of normal thyroid cells (NTHY), as well as monocytes and endothelial cells (HUVEC). EVs’ size/number were analyzed by flow cytometry and confocal microscopy. Gene expression, protein level and localization were investigated by qRT-PCR, WB and ICC/IF, respectively. Proliferation, migration and tube formation were analyzed. When compared with NTHY, CGTH and BcPAP secreted significantly more EVs. Treatment of NTHY with cancer-derived EVs changed the expression of tetraspanin genes, but did not affect proliferation and migration. Cancer-derived EVs suppressed tube formation by endothelial cells and did not affect the phagocytic index of monocytes. The number of 6μm size fraction of cancer-derived EVs correlated negatively with the CD63 and CD81 expression in NTHY cells, as well as positively with angiogenesis in vitro. Thyroid cancer-derived EVs can affect the expression of tetraspanins in normal thyroid cells. It is possible that 6 μm EVs contribute to the regulation of NTHY gene expression and angiogenesis.

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“…Tetraspanin 9 has been reported in gastric cancer to inhibit the growth and invasion of tumor cells via the ERK1/2 signaling pathway. 29,65 The variation of WBC at diagnosis of ALL is very diverse and shows indications of complex underlying feature interactions. Based on our models, it seems that the primary driver of WBC at diagnosis is the disease subtype of ALL, with single germline variants playing a very limited role.…”

Section: Discussionmentioning

confidence: 99%

“…Tetraspanin 9 belongs to a family of transmembrane proteins that mediates signal transduction in processes such as cell adhesion and invasion. Tetraspanin 9 has been reported in gastric cancer to inhibit the growth and invasion of tumor cells via the ERK1/2 signaling pathway 29,65 …”

Section: Discussionmentioning

confidence: 99%

Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype–genotype study

Helenius

Vaitkevičienė

Abrahamsson

et al. 2022

Pediatric Blood & Cancer

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Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well‐known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL‐2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome‐8‐Bead chip) aged 1–45 years, diagnosed with B‐cell precursor (BCP‐) or T‐cell ALL (T‐ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC‐associated germline genetic variants in a genome‐wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (ρBCP‐ALL = −.17, ρT‐ALL = −.19; p < 3 × 10−4). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (ρ = .43, p << 2 × 10−6). However, when the spline‐adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.

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Tetraspanins: Novel Molecular Regulators of Gastric Cancer

Cited by 30 publications

References 99 publications

Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells

Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells

Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?

Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype–genotype study

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