Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

Herr, Michael J.; Longhurst, Celia M.; Baker, Benjamin; Homayouni, Ramin; Speich, Henry E.; Kotha, Jayaprakash; Jennings, Lisa K.

doi:10.1016/j.bbrc.2014.04.046

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…Here, we identified CD9 as a potential AML LSCspecific molecule by analyzing three microarray datasets of AML LSCs and conducting minimal residual disease (MRD) expression profiling. As a member of the tetraspanin family, CD9 is the third most abundant protein on the surface of platelets and is required for the release of microparticles from coated-platelets [13,14]. Furthermore, it was reported that CD9 plays an important role in cell adhesion, movement, differentiation, proliferation, apoptosis, and chemotherapy resistance [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

et al. 2021

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Background Leukemia stem cells (LSCs) are responsible for the initiation, progression, and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs. Methods Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML, and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration, and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance, and migration. Results CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9−) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells. Conclusion Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.

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Section: Introductionmentioning

confidence: 99%

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

et al. 2021

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“…However, controversial results have also been reported. For instance, in lymphoma cell lines, introduction of CD9 expression resulted in significantly increased cell proliferation (30). This discrepancy is not surprising, as tetraspanins have recently been postulated as both cancer suppressors and promoters.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface

et al. 2015

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The expression of CD9 has been shown to be inversely associated with pancreatic cancer metastasis but the underlying mechanism remains incompletely understood. Using the two closely associated pancreatic cancer cell lines, PaTu-8898s and PaTu-8898t, which are metastatic and non-metastatic, respectively, we showed that the PaTu-8988s cells expressed a lower level of CD9 but had higher proliferation and migration rates than the PaTu-8898t cells. An inverse correlation between CD9 expression and the cell surface level of epidermal growth factor receptor (EGFR) was observed in both cell lines. In the PaTu-8898s cells, overexpression of CD9 decreased the cell surface expression of EGFR, associated with increased expression of dynamin-2, whereas in the PaTu-8898t cells, knockdown of CD9 with RNA interference (RNAi) increased the cell surface expression of EGFR, associated with decreased expression of dynamin-2. However, the total EGFR level did not change by manipulation of CD9 expression, suggesting that CD9 plays a role in EGFR endocytosis. Furthermore, in the PaTu-8898ts cells, CD9 overexpression decreased the cell proliferation and migration, which were reversed by EGFR overexpression, whereas in the PaTu-8898t cells, CD9 knockdown enhanced the cell proliferation and migration which were blocked by EGFR RNAi both in vitro and in vivo. Thus, in pancreatic cancer cells, downregulation of CD9 may play a role in cancer growth and metastasis through, at least in part, enhancing cell surface expression of EGFR.

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“…Here, we identi ed CD9 as a potential AML LSC-speci c molecule by analyzing three microarray datasets of AML LSCs and conducting minimal residual disease (MRD) expression pro ling. As a member of the tetraspanin family, CD9 is the third most abundant protein on the surface of platelets and is required for the release of microparticles from coated-platelets [13,14]. Furthermore, it was reported that CD9 plays an important role in cell adhesion, movement, differentiation, proliferation, apoptosis and chemotherapy resistance [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

Liu

Wang

Zhang

et al. 2021

Preprint

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Background: Leukemia stem cells (LSCs) are responsible for the initiation, progression and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs.Methods: Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance and migration.Results: CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9-) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells.Conclusion: Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.

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Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

Cited by 7 publications

References 28 publications

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

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